CHAPTER 17 CYTOSKELETON © 2009
17-1
Garland Science Publisin!
Identify the cytoskeletal structures depicted in the epithelial cells shown in Figure Q17-1.
Figure Q17-1 17-2
Which of the following statements about the cytoskeleton is false? (a) (a) The The cyt cytosk oskele eleton ton is made made up of three three types types of prote protein in filam filamen ent. t. (b) (b) The The bacte bacteri rial al cyto cytoske skele leton ton is imp import ortan antt for for cell cell divis divisio ion n and and DNA DNA segregation. (c) (c) Prote Protein in mono monome mers rs tha thatt are are hel held d toge togethe therr with with coval covalen entt bond bondss form form cytoskeletal filaments. (d) (d) The The cytos cytoskel kelet eton on of of a cell cell can can cha change nge in respon response se to to the the envir environm onmen ent. t.
17-3
Indicate which of the three major classes of cytoskeletal elements each statement below refers to. A. monomer that binds ATP B. incl ncludes kerat ratin and and neurof rofila ilament ents C. impo importa rtant nt for forma formatio tion n of of the the contr contract actile ile ring ring during during cyto cytokin kinesi esiss D. supp suppor orts ts and and str stren engt gthe hens ns the the nucl nuclea earr enve envelo lope pe E. their st stability in involves a GTP ca cap F. used in the eucaryotic fl flagellum G. a component of the the mitotic otic spind indle H. can be be co connected ted th throu rough de desmosom somes I. dire irectly tly involv olved in musc uscle cont ontrac raction J. abundant in filopodia
17-4
Which of the following statements about the cytoskeleton is true? (a) (a) All All eucar eucaryot yotic ic cell cellss have have actin actin,, micro microtub tubule ules, s, and and interm intermedi ediate ate fila filame ments nts in their cytoplasm.
(b) (b) (c) (c) (d) (d)
17-5
The The cytos cytoskel kelet eton on provi provide dess a rigid rigid and and unch unchang angea eable ble struc structur turee impo importa rtant nt for the shape of the cell. The The three three cytos cytoske kelet letal al fila filame ment ntss perfo perform rm dist distinc inctt tasks tasks in the the cel celll and and act act completely independently of one another. Actin Actin filam filament entss and and micr microtu otubu bules les have have an an inher inheren entt pola polarit rity, y, with with a plus plus end that grows more quickly than the minus end.
Rank the following cytoskeletal filaments from smallest to largest in diameter (1 = smallest in diameter, 4 = largest) ______ intermediate filaments ______ microtubules ______ actin filament ______ myofibril
"n#er$edia#e %ila$en#s 17-6
Which of the statements below about intermediate filaments is false? (a) (a) They They can can stay stay intact intact in cells cells treate treated d with with conce concentr ntrate ated d salt salt solu solutio tions. ns. (b) (b) They They can can be be fou found nd in the the cyt cytop opla lasm sm and and the the nucl nucleu eus. s. (c) (c) They They can can be be anch anchore ored d to the the plas plasma ma mem membra brane ne at at cel cell-c l-cel elll junc junctio tion. n. (d) Each filament is is about 10 µ m in diameter.
17-7
Intermediate filaments are made from elongated fibrous proteins that are assembled into a ropelike structure. Figure Q17-7 shows the structure of an intermediate filament subunit. You are interested in how intermediate filaments are formed, and you create an intermediate filament subunit whose α -helical region is twice as long as that of a normal intermediate filament by duplicating the normal α-helical region while keeping a globular head at the N-terminus and a globular globular tail at the C-terminu C-terminus; s; you call this this subunit IF IF α d. If you were were to assemble assemble intermediate intermediate filaments filaments using using IF2 α d as the subunit, which which of the the following following predictions below describes the most likely outcome?
Figure Q17-7 (a) (a) (b) (b) (c) (c)
Fila Filame ment ntss asse assemb mble led d usin using g IF α d will will int inter erac actt with with dif diffe fere rent nt cyt cytos oske kele leta tall components. Fila Filame ment ntss asse assemb mble led d usi using ng IF α d wil willl for form m dim dimer erss tha thatt are are twic twicee as as lon long g as as dimers assembled from normal intermediate filaments. Sixt Sixtee een n tet tetra rame mers rs ass assem embl bled ed from from IF α d wil willl be be nee neede ded d for for a rop ropel elik ikee structure to form.
(b) (b) (c) (c) (d) (d)
17-5
The The cytos cytoskel kelet eton on provi provide dess a rigid rigid and and unch unchang angea eable ble struc structur turee impo importa rtant nt for the shape of the cell. The The three three cytos cytoske kelet letal al fila filame ment ntss perfo perform rm dist distinc inctt tasks tasks in the the cel celll and and act act completely independently of one another. Actin Actin filam filament entss and and micr microtu otubu bules les have have an an inher inheren entt pola polarit rity, y, with with a plus plus end that grows more quickly than the minus end.
Rank the following cytoskeletal filaments from smallest to largest in diameter (1 = smallest in diameter, 4 = largest) ______ intermediate filaments ______ microtubules ______ actin filament ______ myofibril
"n#er$edia#e %ila$en#s 17-6
Which of the statements below about intermediate filaments is false? (a) (a) They They can can stay stay intact intact in cells cells treate treated d with with conce concentr ntrate ated d salt salt solu solutio tions. ns. (b) (b) They They can can be be fou found nd in the the cyt cytop opla lasm sm and and the the nucl nucleu eus. s. (c) (c) They They can can be be anch anchore ored d to the the plas plasma ma mem membra brane ne at at cel cell-c l-cel elll junc junctio tion. n. (d) Each filament is is about 10 µ m in diameter.
17-7
Intermediate filaments are made from elongated fibrous proteins that are assembled into a ropelike structure. Figure Q17-7 shows the structure of an intermediate filament subunit. You are interested in how intermediate filaments are formed, and you create an intermediate filament subunit whose α -helical region is twice as long as that of a normal intermediate filament by duplicating the normal α-helical region while keeping a globular head at the N-terminus and a globular globular tail at the C-terminu C-terminus; s; you call this this subunit IF IF α d. If you were were to assemble assemble intermediate intermediate filaments filaments using using IF2 α d as the subunit, which which of the the following following predictions below describes the most likely outcome?
Figure Q17-7 (a) (a) (b) (b) (c) (c)
Fila Filame ment ntss asse assemb mble led d usin using g IF α d will will int inter erac actt with with dif diffe fere rent nt cyt cytos oske kele leta tall components. Fila Filame ment ntss asse assemb mble led d usi using ng IF α d wil willl for form m dim dimer erss tha thatt are are twic twicee as as lon long g as as dimers assembled from normal intermediate filaments. Sixt Sixtee een n tet tetra rame mers rs ass assem embl bled ed from from IF α d wil willl be be nee neede ded d for for a rop ropel elik ikee structure to form.
(d) (d)
17-8
Dime Dimers rs of of IF IF αd wil willl for form m by by int inter erac acti tion onss with with the the N-t N-ter ermi mina nall glo globu bula larr head and the C-terminal globular tail.
For each of the following sentences, fill in the blanks with the best word or phrase selected from the list below. Not all words or phrases will be used; use each word or phrase only once. Intermediate filaments are found mainly in cells that are subject to mechanical stress. Mutations in genes that disrupt intermediate filaments cause some rare human diseases. For example, the skin of people with epidermolysis bullosa simplex is very susceptible to mechanical injury; people with this disorder have mutations in their __________________ genes, the intermediate filament found in epithelial cells. These filaments are usually connected from cell to cell through junctions called __________________s. The main filaments found in muscle cells belong to the __________________ family; people with disruptions in these intermediate filaments can have muscular dystrophy. In the nervous system, __________________s help strengthen the extremely long extensions often present in nerve cell axons; disruptions in these intermediate filaments can lead to neurodegeneration. People who carry mutations in the gene for __________________, an important protein for cross-linking intermediate filaments, have a disease that combines symptoms of epidermolysis bullosa simplex, muscular dystrophy, and neurodegeneration. desmosome keratin kinase
17-9
lamin neurofilament plectin
synapse vimentin
Match the type of intermediate filament with its appropriate location. lamins _________ A. nerve cells neur neurof ofil ilam amen ents ts ____ ______ ____ ___ _ B. epit epithe heli liaa vimentins __ _________ C. nu nucleus keratins _________ D. connective tissue
17-10 Keratins, neurofilaments, and vimentins are all categories of intermediate filaments. Which of the following properties below is not true true of these types of intermediate filaments? (a) (a) They They stre streng ngth then en cell cellss aga again inst st mech mechan anic ical al stre stress ss.. (b) (b) Dime Dimers rs assoc associa iate te by nonco noncoval valen entt bon bondi ding ng to form form a tetram tetramer. er. (c) They are are found und in the the cyto ytoplas lasm. (d) (d) Phosph Phosphor oryla ylatio tion n cause causess disas disassem sembl bly y durin during g every every mito mitotic tic cycle cycle..
17-11 Phosphorylation of nuclear lamins regulates their assembly and disassembly during mitosis. You add a drug to cells undergoing mitosis that inhibits the activity of an enzyme that dephosphorylates nuclear lamins. What do you predict will happen to these cells? Why? 17-12 You are interested in understanding the regulation of nuclear lamina assembly. To create an in vitro system for studying this process you start with partly purified nuclear lamina subunits to which you will add back purified cellular components to drive nuclear lamina assembly. Before you start doing experiments, your instructor suggests that you consider what type of conditions would be most amenable to the assembly of nuclear lamina from its individual subunits in vitro. Which of the following conditions do you predict would be most likely to enhance the assembly of the nuclear lamina? (a) addition of phosphatase inhibitors (b) addition of ATP (c) addition of a concentrated salt solution that is 10 times the concentration normally found in the nucleoplasm (d) addition of protein kinase inhibitors
&icr'#ubules 17-13 Place the following in order of size, from the smallest to the largest. A. protofilament B. microtubule α-tubulin C. D. tubulin dimer E. mitotic spindle 17-14 In the three cell outlines in Figure Q17-14, indicate the arrangement of the microtubules, showing clearly their free and attached ends. On each figure indicate the plus end and the minus end for one of the microtubules.
Figure Q17-14 17-15 Which of the following statements about microtubules is true? (a) Motor proteins move in a directional fashion along microtubules by using the inherent structural polarity of a protofilament. (b) The centromere nucleates the microtubules of the mitotic spindle. (c) Because microtubules are subject to dynamic instability, they are used only for transient structures in a cell. (d) ATP hydrolysis by a tubulin heterodimer is important for controlling the growth of a microtubule. 17-16 For each of the following sentences, fill in the blanks with the best word or phrase selected from the list below. Not all words or phrases will be used; use each word or phrase only once.
Microtubules are formed from the tubulin heterodimer, which is composed of the nucleotide-binding __________________ protein and the __________________ protein. Tubulin dimers are stacked together into protofilaments; __________________ parallel protofilaments form the tubelike structure of a microtubule. __________________ rings are important for microtubule nucleation and are found in the __________________ , which is usually found near the cell’s nucleus in cells that are not undergoing mitosis. A microtubule that is quickly growing will have a __________________ cap that helps prevent the loss of subunits from its growing end. Stable microtubules are used in cilia and flagella; these microtubules are nucleated from a __________________ and involve a “__________________ plus two” array of microtubules. The motor protein __________________ generates the bending motion in cilia; the lack of this protein can cause Kartagener’s syndrome in humans. basal body myosin dynein GTP twenty-one α-tubulin
γ -tubulin UTP thirteen centrosome δ -tubulin kinesin
ATP nine β -tubulin four vimentin two
17-17 The hydrolysis of GTP to GDP carried out by tubulin molecules ________________. (a) provides the energy needed for tubulin to polymerize (b) occurs because the pool of free GDP has run out (c) tips the balance in favor of microtubule assembly (d) allows the behavior of microtubules called dynamic instability 17-18 The microtubules in a cell form a structural framework that can have all the following functions except which of the following? (a) holding internal organelles such as the Golgi apparatus in particular positions in the cell (b) creating long thin cytoplasmic extensions that protrude from one side of the cell (c) strengthening the plasma membrane (d) moving materials from one place to another inside a cell 17-19 You are curious about the dynamic instability of microtubules and decide to join a lab that works on microtubule polymerization. The people in the lab help you grow some microtubules in culture using conditions that allow you to watch individual microtubules under a microscope. You can see the microtubules growing and shrinking, as you expect. The professor who runs the lab gets in a new piece of equipment, a very fine laser beam that can be used to sever microtubules. She is very excited and wants to sever growing microtubules at their middle, using the laser beam. A. Do you predict that the newly exposed microtubule plus ends will grow or shrink? Explain your answer. B. What do you expect would happen to the newly exposed plus ends if you were to grow the microtubules in the presence of an analog of GTP that cannot be hydrolyzed, and you then severed the microtubules in the middle with a laser beam? 17-20 Which of the following statements regarding dynamic instability is false? (a) Each microtubule filament grows and shrinks independently of its neighbors. (b) The GTP cap helps protect a growing microtubule from depolymerization. (c) GTP hydrolysis by the tubulin dimer promotes microtubule shrinking. (d) The newly freed tubulin dimers from a shrinking microtubule can be immediately captured by growing microtubules and added to their plus end. 17-21 Which of the situations below will enhance microtubule shrinkage? (a) addition of a drug that inhibits GTP exchange on free tubulin dimers (b) addition of a drug that inhibits GTP hydrolysis of tubulin dimers
(c) (d)
addition of a drug that increases the affinity of tubulin molecules carrying GDP for other tubulin molecules addition of a drug that blocks the ability of a tubulin dimer to bind to γ tubulin
17-22 The graph in Figure Q17-22 shows the time course of the polymerization of pure tubulin in vitro. You can assume that the starting concentration of free tubulin is much higher than it is in cells.
Figure Q17-22 A. B.
Explain the reason for the initial lag in the rate of microtubule formation. Why does the curve level out after point C?
17-23 Which of the following statements about organellar movement in the cell is false? (a) Organelles undergo saltatory movement in the cell. (b) Only the microtubule cytoskeleton is involved in organellar movement. (c) Motor proteins involved in organellar movement use ATP hydrolysis for energy. (d) Organelles are attached to the tail domain of motor proteins. 17-24 Microtubules are important for transporting cargo in nerve cell axons, as diagrammed in Figure Q17-24. Notice that the two types of cargo are traveling in opposite directions. Which of the following statements is likely to be false?
Figure Q17-24 (a) (b) (c) (d)
The gray cargo is attached to dynein. The black cargo and the gray cargo require ATP hydrolysis for their motion. The black cargo moving toward the axon terminal contains a domain that specifically interacts with the tail domain of a particular kind of motor. The black cargo and the gray cargo are moving along microtubules of opposite polarity.
17-25 Do you agree or disagree with this statement? Explain your answer.
Minus end-directed microtubule motors (like dyneins) deliver their cargo to the periphery of the cell, whereas plus end-directed microtubule motors (like kinesins) deliver their cargo to the interior of the cell. 17-26 Which of the following statements is correct? Kinesins and dyneins ____________________. (a) have tails that bind to the filaments (b) move along both microtubules and actin filaments (c) often move in opposite directions to each other (d) derive their energy from GTP hydrolysis 17-27 Match the following labels to the numbered lines on Figure Q17-27.
Figure Q17-27 A. B. C. D.
minus end of microtubule tail of motor protein cargo of motor protein head of motor protein
Which of the two motors in Figure Q17-27 is most probably a kinesin? Explain your answer. 17-28 Some lower vertebrates such as fish and amphibians can control their color by regulating specialized pigment cells called melanophores. These cells contain small, pigmented organelles, termed melanosomes, that can be dispersed throughout the cell, making the cell darker, or aggregated in the center of the cell to make the cell lighter. You purify the melanosomes from melanophores that have either aggregated or dispersed melanosomes and find that: 1. aggregated melanosomes co-purify with dynein; 2. dispersed melanosomes co-purify with kinesin.
Given this set of data, propose a mechanism for how the aggregation and dispersal of melanosomes occur. 17-29 Indicate whether each of the following statements refers to a ciliary microtubule, a microtubule of the mitotic spindle, both types of microtubule, or neither type of microtubule. A. The basal body is the organizing center. B. The monomer is sequestered by profilin. C. It is arranged in a “9 + 2” array. D. It is nucleated at the centrosome. E. It uses dynein motors. F. It is involved in sperm motility. G. It is involved in moving fluid over the surface of cells. 17-30 Which of the following items below are not important for flagellar movement? (a) sarcoplasmic reticulum (b) ATP (c) dynein (d) microtubules 17-31 Figure Q17-31A shows how the movement of dynein causes the flagellum to bend. If instead of the normal situation, the polarity of the adjacent doublet of microtubules were to be reversed (see Figure Q17-31B) what do you predict would happen?
Figure Q17-31 (a) (b) (c) (d)
No bending would occur. Bending would occur exactly as diagrammed in Figure Q17-31A. Bending would occur, except that the right microtubule doublet would move down relative to the left one. The two microtubule doublets would slide away from each other.
17-32 Figure Q17-32 shows two isolated outer doublet microtubules from a eucaryotic flagellum with their associated dynein molecules.
Figure Q17-32 A. B. C.
Sketch what will happen to this structure if it is supplied with ATP. Sketch what will happen to this structure if the linking proteins are removed and it is supplied with ATP. In a complete flagellum, what would happen if all the dynein molecules were active at the same time?
Ac#in %ila$en#s 17-33 Which of the following statements about actin is false? (a) ATP hydrolysis decreases actin filament stability. (b) Actin at the cell cortex helps govern the shape of the plasma membrane.
(c) (d)
Actin filaments are nucleated at the side of existing actin filaments in lamellipodia. The dynamic instability of actin filaments is important for cell movement.
17-34 For each of the following sentences, fill in the blanks with the best word or phrase selected from the list below. Not all words or phrases will be used; use each word or phrase only once.
There are many actin-binding proteins in cells that can bind to actin and modify its activity. Some proteins such as __________________ bind to actin monomers, sequestering them until needed for filament formation. __________________ proteins bind to the end of actin filaments. The __________________ proteins are important for nucleation of the branched actin structures commonly found in the __________________ of moving cells, whereas __________________ proteins are important for the formation of unbranched actin filaments commonly found in __________________. Proteins belonging to the __________________ family of GTPases regulate changes in the actin cytoskeleton in response to extracellular signals. capping integrin filopodia Rho severing
lamellipodia ARP bundling gelsolin cytochalasin
thymosin formin GAP contracting lamin
17-35 Do you agree or disagree with the following statement? Explain your answer.
Nucleotide hydrolysis has a similar role in actin polymerization and in tubulin polymerization. 17-36 Actin-binding proteins bind to actin and can modify its properties. You purify a protein, Cap1, that seems to bind and cap one end of an actin filament, although you do not know whether it binds the plus end or the minus end. To determine which end of the actin filament your protein binds to, you decide to examine the effect of Cap1 on actin polymerization by measuring the kinetics of actin filament formation in the presence and the absence of Cap1 protein. You obtain the following results (see Figure Q17-36). Do you think Cap1 binds the plus end or the minus end of actin? Explain your reasoning.
Figure Q17-36 17-37 In the cell, the concentration of actin monomer is higher than the concentration required for purified actin monomers to polymerize in vitro. Thymosin is a protein that can bind actin monomers. If you were to add a drug that inhibits the ability of thymosin to bind actin monomers, what effect would this have on actin polymerization? Explain your answer. 17-38 Which of the following statements is false? (a) Cytochalasins prevent actin polymerization. (b) Actin filaments are usually excluded from the cell cortex. (c) Integrins are transmembrane proteins that can bind to the extracellular matrix. (d) ARPs can promote the formation of branched actin filaments. 17-39 Cell movement involves the coordination of many events in the cell. Which of the following phenomena are not required for cell motility? (a) Myosin-mediated contraction at the rear of the moving cell. (b) Integrin association with the extracellular environment. (c) Nucleation of new actin filaments. (d) Release of Ca 2+ from the sarcoplasmic reticulum. 17-40 The following proteins are important for cell movement. Match the following proteins with their function. myosin II _________ A. nucleation of new actin filaments ARP proteins _________ B. regulation of the availability of actin monomers profilin _________ C. involvement in focal contacts integrins _________ D. contracting the rear of the cell 17-41 Figure Q17-41 a lamellipodium. statements is false?
shows the leading edge of Which of the following
Figure Q17-41 (a) (b) (c) (d)
Nucleation of new filaments near at the leading edge pushes the plasma membrane forward. ARP proteins nucleate the branched actin filaments in the lamellipodia. Capping proteins bind to the minus end of actin filaments. There is more ATP-bound actin at the leading edge than in the actin filaments away from the leading edge.
17-42 You are examining a cell line in which activation of the Rho family member Rac promotes lamellipodia formation. Which of the following statements is most likely to be true? (a) Cells carrying a Rac mutation that makes Rac act as if it is always bound to GTP will polymerize more unbranched actin filaments than normal cells. (b) Cells carrying a Rac mutation that makes Rac unable to exchange GDP for GTP will polymerize more unbranched actin filaments than normal cells. (c) Cells carrying a Rac mutation that makes Rac act as if it is always bound to GTP will polymerize more branched actin filaments than normal cells. (d) Cells carrying a Rac mutation that makes Rac unable to exchange GDP for GTP will polymerize more branched actin filaments than normal cells. 17-43 In the budding yeast, activation of the GTP-binding protein Cdc42 occurs on binding of an external signal (pheromone) to a G-protein-linked receptor. Activation of Cdc42 promotes actin polymerization. Predict would happen to actin polymerization, in comparison with pheromone-treated cells, in the following cases. A. You add pheromone to an inhibitor of G-protein-linked receptors. B. You add pheromone to a nonhydrolyzable analogue of GTP. 17-44 Your friend works in a biotech company that has just discovered a drug that seems to promote lamellipodia formation in cells. Which of the following molecules below is unlikely to be involved in the pathway that this drug affects?
(a) (b) (c) (d)
Rac ARP actin myosin
&uscle C'n#rac#i'n 17-45 Which of the following structures shorten during muscle contraction? (a) myosin filaments (b) flagella (c) sarcomeres (d) actin filaments 17-46 Which of the following conditions below is likely to decrease the likelihood of skeletal muscle contraction? (a) partial depolarization of the T-tubule membrane, such that the resting potential is closer to zero (b) addition of a drug that blocks Ca 2+ binding to troponin (c) an increase in the amount of ATP in the cell (d) a mutation in tropomyosin that decreases its affinity for the actin filament 17-47 Which of the following statements about skeletal muscle contraction is false? (a) When a muscle cell receives a signal from the nervous system, voltagegated channels open in the T-tubule membrane. (b) The changes in voltage across the plasma membrane that occur when a muscle cell receives a signal from the nervous system cause an influx of Ca2+ into the sarcoplasmic reticulum, triggering a muscle contraction. (c) A change in the conformation of troponin leads to changes in tropomyosin such that it no longer blocks the binding of myosin heads to the actin filament. (d) During muscle contraction, the Z discs move closer together as the myosin heads walk toward the plus ends of the actin filaments. 17-48 Do you agree or disagree with the following statement? Explain your answer.
When skeletal muscle receives a signal from the nervous system to contract, the signal from the motor neuron triggers the opening of a voltage-sensitive Ca 2+ channel in the muscle cells’ plasma membrane, allowing Ca 2+ to flow into the cell. 17-49 You isolate some muscle fibers to examine what regulates muscle contraction. When you bathe the muscle fibers in a solution containing ATP and Ca 2+, you see muscle contraction (experiment 3 in Table Q17-49). Ca 2+ is necessary, as
solutions containing ATP alone or nothing do not stimulate contraction and thus the muscle remains in a relaxed state (experiments 1 and 2 in Table Q17-49). From what you know about the mechanism of muscle contraction, fill in your predictions of whether the muscle will be contracted or relaxed for experiments 4, 5, and 6. Explain your answers.
Table Q17-49 Extra credit: In what state would the muscle be if you added Ca 2+ but no ATP?
H'( )e Kn'(* Pursuin! &'#'r Pr'#eins 17-50 Consider the in vitro motility assay using purified kinesin and purified polymerized microtubules shown in Figure Q17-50. The three panels are images taken at 1 second intervals. In this figure, three microtubules have been numbered to make it easy to identify them. Which of the following statements about this assay is false?
Figure Q17-50 (a)
Kinesin molecules are attached by their tails to a glass slide.
(b)
(c) (d)
The microtubules used in this assay must be polymerized using conditions that stabilize tubule formation or else they would undergo dynamic instability. ATP must be added for this assay to work. Addition of the nonhydrolyzable ATP analog (AMP-PNP) would cause the microtubules to move faster.
17-51 You are interested in studying kinesin movements. You therefore prepare silica beads and coat them with kinesin molecules so that each bead, on average, has only one kinesin molecule attached to it. You add these kinesin-coated beads to a preparation of microtubules you have polymerized. Using video microscopy, you watch the kinesin move down the microtubules. A. Kinesin-GFP has been measured to move along microtubules at a rate of 0.3 µ m/sec, and single-molecule studies have revealed that kinesin moves along microtubules progressively, with each step being 8 nm. How many steps can the kinesin molecule take in 4 seconds, assuming that the kinesin stays attached to the microtubule for the entire 4 seconds? B. Because each kinesin molecule is thought to take approximately 100 steps before falling off the microtubule, will you see your silica beads detach from the microtubule during your 4 seconds of observation? C. What would you predict would happen to the kinesin-coated silica beads if you were to add AMP-PNP (a nonhydrolyzable ATP analog)?
CHAPTER 1+ THE CELL ,"-"S"ON CYCLE © 2009
Garland Science Publisin!
O.er.ie( '/ #e Cell Ccle 18-1
For each of the following sentences, fill in the blanks with the best word or phrase selected from the list below. Not all words or phrases will be used; use each word or phrase only once.
The four phases of the cell cycle, in order, are G 1, __________________, __________________, and __________________. A cell contains the most DNA after __________________ phase of the cell cycle. A cell is smallest in size after __________________ phase of the cell cycle. Growth occurs in __________________, __________________, and __________________ phases of the cell cycle. A cell does not enter mitosis until it has completed __________________ synthesis. DNA G1 G2
M nucleotide organelle
protein S
18-2
What would be the most obvious outcome of repeated cell cycles consisting of S phase and M phase only? (a) Cells would not be able to replicate their DNA. (b) The mitotic spindle could not assemble. (c) Cells would get larger and larger. (d) The cells produced would get smaller and smaller.
18-3
A mutant yeast strain stops proliferating when shifted from 25 °C to 37°C. When these cells are analyzed at the two different temperatures, using a machine that sorts cells according to the amount of DNA they contain, the graphs in Figure Q18-3 are obtained.
Figure Q18-3 Which of the following would not explain the results with the mutant? (a) inability to initiate DNA replication (b) inability to begin M phase (c) inability to activate proteins needed to enter S phase (d) inappropriate production of a signal that causes the cells to remain in G 1 18-4
Which of the following events does not usually occur during interphase? (a) Cells grow in size. (b) The nuclear envelope breaks down. (c) DNA is replicated. (d) The centrosomes are duplicated.
18-5
What would happen to the progeny of a cell that proceeded to mitosis and cell division after entering S phase but had not completed S phase? Keep in mind that highly condensed chromatin, including the centromere region, is replicated late in S phase. Explain your answer.
18-6
Are the statements below true or false? Explain your answer. Statement 1: Generally, in a given organism, the S, G 2, and M phases of A. the cell cycle take a defined and stereotyped amount of time in most cells.
B.
Statement 2: Therefore, the cell-cycle control system operates primarily by a timing mechanism, in which the entry into one phase starts a timer set for sufficient time to complete the required tasks. After a given amount of time has elapsed, a molecular “alarm” triggers movement to the next phase.
18-7
Which of the following statements about the cell cycle is false? (a) Once a cell decides to enter the cell cycle, the time from start to finish is the same in all eucaryotic cells. (b) An unfavorable environment can cause cells to arrest in G 1. (c) A cell has more DNA during G 2 than it did in G1. (d) The cleavage divisions that occur in an early embryo have short G 1 and G2 phases.
18-8
Which of the following descriptions is consistent with the behavior of a cell that lacks a protein required for a checkpoint mechanism that operates in G 2? (a) The cell would be unable to enter M phase. (b) The cell would be unable to enter G 2. (c) The cell would enter M phase under conditions when normal cells would not. (d) The cell would pass through M phase more slowly than normal cells.
H'( )e Kn'(* ,isc'.er '/ Cclins and Cds 18-9
For each of the following sentences, fill in the blanks with the best word or phrase selected from the list below. Not all words or phrases will be used; each word or phrase should be used only once. Many features of __________________ cells make them suitable for biochemical studies of the cell-cycle control system. For example, the cells are unusually large and are arrested in a __________________-like phase. When the cells are triggered to resume cycling, the cell divisions have especially __________________ G 1 and G2 phases and occur __________________. Studies with Xenopus eggs identified a partly purified activity called __________________ that drives a resting Xenopus oocyte into M phase. MPF activity was found to __________________ during the cell cycle, although the amount of its kinase component, called __________________, remained constant. The regulatory component of MPF, called __________________, has a __________________ effect on MPF activity and plays a part in regulating interactions with its __________________s. The components of MPF are evolutionarily __________________ from yeast to humans, so that
the corresponding human genes are __________________ to function in yeast. able asynchronously Cdk conserved cyclin divergent egg fibroblast G1 G2
hexokinase inhibitory long M maturation promoting factor oscillate PI 3-kinase regulin S
short sperm steady stimulatory substrate synchronously ubiquitin unable uniform
18-10 MPF activity was discovered when cytoplasm from a Xenopus M-phase cell was injected into Xenopus oocytes, inducing the oocytes to form a mitotic spindle. In a control experiment, Xenopus interphase cytoplasm was injected into oocytes and shown not to induce the formation of a mitotic spindle. Which of the following statements is not a legitimate conclusion from the control experiment? (a) The piercing of the oocyte membrane by a needle is insufficient to cause mitotic spindle formation. (b) An increased volume of cytoplasm is insufficient to cause mitotic spindle formation. (c) Injection of extra RNA molecules is insufficient to cause mitotic spindle formation. (d) Components of an interphase nucleus are insufficient to cause mitotic spindle formation. 18-11 Which of the following is not good direct evidence that the cell-cycle control system is conserved through billions of years of divergent evolution? (a) A yeast cell lacking Cdk function can use the human Cdk to substitute for its missing Cdk during the cell cycle. (b) The amino acid sequences of cyclins in plants are similar to the amino acid sequences of cylins in humans. (c) The Cdk proteins in humans share conserved phosphorylation sites with the Cdk proteins in yeast. (d) Yeast cells have only one Cdk, whereas humans have many Cdks.
Te CellCcle C'n#r'l Ss#e$ 18-12 Levels of Cdk activity change during the cell cycle, in part, because ________________. (a) the Cdks phosphorylate each other (b) the Cdks activate the cyclins
(c) (d)
Cdk degradation precedes entry into the next phase of the cell cycle cyclin levels change during the cycle
18-13 The concentration of mitotic cyclin (M cyclin) ________________. (a) rises markedly during M phase (b) is activated by phosphorylation (c) falls toward the end of M phase as a result of ubiquitylation and degradation (d) is highest in G 1 phase 18-14 You have isolated a strain of mutant yeast cells that divides normally at 30 °C but cannot enter M phase at 37 °C. You have isolated its mitotic cyclin and mitotic Cdk and find that both proteins are produced and can form a normal M-Cdk complex at both temperatures. Which of the following temperature-sensitive mutations could not be responsible for the behavior of this strain of yeast? (a) inactivation of a protein kinase that acts on the mitotic Cdk kinase (b) inactivation of an enzyme that ubiquitylates M cyclin (c) inactivation of a phosphatase that acts on the mitotic Cdk kinase (d) a decrease in the levels of a transcriptional regulator required for producing sufficient amounts of M cyclin 18-15 Match the following labels to the numbered label lines on Figure Q18-15.
Figure Q18-15 A. B. C. D. E. F. G. H.
G1 phase mitotic cyclin mitotic Cdk S phase S-phase cyclin S-phase Cdk MPF G2 phase
18-16 You have isolated a mutant in which a fraction of the new cells die soon after cell division and a fraction of the living cells have an extra copy of one or more
chromosomes. When you grow the cells under conditions in which they transit the cell cycle more slowly, the defect disappears, suggesting that the mitotic spindle and segregation machinery are normal. Propose a basis for the defect. 18-17 Cells in the G0 state ________________. (a) do not divide (b) cannot not re re-en -enter ter th the ce cell cycle (c) (c) have have ente entere red d thi thiss arr arres estt sta state te from from eith either er G 1 or G2 (d) have duplicated th their DNA 18-18 What is the main molecular difference between cells in a G 0 state and cells that have simply paused in G 1?
S Pase 18-19 You create cells with a version of Cdc6 that cannot be phosphorylated and thus cannot be degraded. Which of the following statements describes the likely consequence of this change in Cdc6? (a) (a) Cell Cellss wil willl ent enter er S phas phasee prem premat atur urel ely. y. (b) (b) Cell Cellss wil willl be be una unabl blee to to com compl plet etee DNA DNA synt synthe hesi sis. s. (c) (c) The The orig origin in rec recog ognit nition ion comp comple lex x (ORC (ORC)) will will be unabl unablee to bind bind to to DNA. DNA. (d) (d) Cdc6 Cdc6 wil willl be pro produ duce ced d inap inappr prop opri riat atel ely y duri during ng M pha phase se.. 18-20 Which of the following statements is false? (a) (a) DNA DNA syn synth thes esis is begi begins ns at orig origin inss of of rep repli lica cati tion on.. (b) (b) The The loadi loading ng of of the the origi origin n reco recogn gniti ition on com comple plexe xess (ORC (ORCs) s) is is trigg trigger ered ed by by SCdk. (c) (c) The The phosp phosphor horyla ylati tion on and and degr degrad adati ation on of of Cdc6 Cdc6 hel help p to ens ensure ure that that DNA DNA is replicated only once in each cell cycle. (d) (d) DNA DNA synth synthesi esiss can can only only begi begin n after after pre-re pre-repl plica icati tive ve comp complex lexes es asse assemb mbles les on the ORCs. 18-21 At the end of DNA replication, the sister chromatids are held together by the ___________. (a) kinetochores (b) securins (c) cohesins (d) histones 18-22 Irradiated mammalian cells usually stop dividing and arrest at a G 1 checkpoint. Place the following events in the order in which they occur. A. production of p21 B. DNA damage C. inhi nhibiti ition of cy cyclin lin–Cdk comple plexes
D.
accumu umulati latio on an and ac activat vation of of p5 p53
18-23 The G1 DNA damage checkpoint ________________. (a) (a) caus causes es cell cellss to to pro proce ceed ed thro throug ugh h S pha phase se more more quic quickl kly y (b) invo nvolves ves the the degrad radation ion of of p5 p53 (c) (c) is acti activa vate ted d by by err error orss cau cause sed d dur durin ing g DNA DNA repl replic icat atio ion n (d) (d) invo involv lves es the the inh inhib ibit itio ion n of cyc cycli lin– n–Cd Cdk k comp comple lexe xess by p21 p21
& Pase 18-24 For each of the following sentences, fill in the blanks with the best word or phrase selected from the list below. Not all words or phrases will be used; each word or phrase should be used only once.
The cell cycle consists of an alternation between __________________, which appears as a period of dramatic activity under the microscope, and a preparative period called __________________, which consists of three phases called __________________, __________________, and __________________. During M phase, the nucleus divides in a process called __________________, and the cytoplasm splits in two in a process called __________________. The cell-cycle control system relies on sharp increases in the activities of regulatory protein called __________________, or __________________, to trigger S and M phases. Inactivation of __________________ is required to exit from M phase after chromosome segregation. APC Cdks condensation cyclin-dependent kinases cytokinesis G1 ph phase G1-Cdk
G2 ph phase interphase intraphase kinesins M phase M-Cdk meiosis
metaphase microtubules mitosis myosins S phase S-Cdk
18-25 Which of the following does not occur during M phase in animal cells? (a) growth of the cell (b) conde ndensat sation of chro hromosom somes (c) brea reakdown own of nuclear ear envelop lope (d) (d) atta attach chme ment nt of chro chromo moso some mess to micr microt otub ubul ules es 18-26 Which of the following statements is false?
(a) (a) (b) (b) (c) (c) (d) (d)
Mitoti Mitoticc Cdk Cdk must must be be phosp phospho horyl rylate ated d by an act activa ivatin ting g kina kinase se (Ca (Cak) k) befo before re it is active. Phosph Phosphor oryla ylatio tion n of mito mitotic tic Cdk Cdk by the inhib inhibito itory ry kina kinase se (Wee (Wee1) 1) mak makes es the the Cdk inactive, even if it is phosphorylated by the activating kinase. Activ Activee M-Cd M-Cdk k phos phospho phory rylat lates es the the act activa ivatin ting g phosp phospha hatas tasee (Cdc (Cdc25) 25) in a positive feedback loop. The The activ activat ating ing pho phosph sphata atase se (Cd (Cdc2 c25) 5) remo remove vess all pho phosph sphate atess from from mito mitotic tic Cdk so that M-Cdk will be active.
18-27 Condensins ________________. (a) (a) are are degr degrad aded ed when hen cel cells ls ente enterr M-p M-pha hase se (b) (b) assem assembl blee into into comp complex lexes es on the the DNA DNA when when phosp phosphor horyla ylate ted d by by M-Cd M-Cdk k (c) (c) are are inv invol olve ved d in in hol holdi ding ng sist sister er chro chroma mati tids ds toge togeth ther er (d) (d) bind bind to DNA DNA bef befor oree DN DNA rep repli lica cati tion on beg begin inss 18-28 Which of the following statements is true? (a) (a) The The mito mitotic tic spind spindle le is largel largely y mad madee of of int interm ermedi ediate ate filam filamen ents. ts. (b) (b) The The contr contrac actil tilee ring ring is mad madee large largely ly of micr microtu otubu bules les and and act actin in filam filament ents. s. (c) (c) The The con contr trac acti tile le ring ring divi divide dess the the nucl nucleu euss in in two two.. (d) (d) The The mito mitotic tic spin spindle dle helps helps segre segrega gate te the the chrom chromos osom omes es to the two two dau daugh ghter ter cells.
&i#'sis 18-29 Which stage of mitosis in an animal cell does each part of Figure Q18-29 represent?
Figure Q18-29 18-30 Figure Q18-30 shows a living cell from the lung epithelium of a newt at different stages in M phase. Order these light micrographs into the correct sequence and identify the stage in M phase that each represents.
Figure Q18-30 18-31 Name the stage of M phase in which the following events occur. Place the numbers 1–8 next to the letter headings to indicate the normal order of events. A. alignment of the chromosomes at the spindle equator B. attachment of spindle microtubules to chromosomes C. breakdown of nuclear envelope D. pinching of cell in two E. separation of two centrosomes and initiation of mitotic spindle assembly F. re-formation of the nuclear envelope G. condensation of the chromosomes H. separation of sister chromatids 18-32 The principal microtubule organizing center in animal cells is the ____________. (a) centrosome (b) centromere (c) kinetochore (d) cell cortex
18-33 Examine the schematic representation of centrosome duplication in Figure Q1833. By analogy with DNA replication, would you classify centrosome duplication as conservative or semi-conservative? Explain your answer.
Figure Q18-33
18-34 Before chromosomes segregate in M phase, they and the segregation machinery must be appropriately prepared. Indicate whether the following statements are true or false. If false, change a single noun to make the statement true. A. Sister chromatids are held together by condensins from the time they arise by DNA replication until the time they separate at anaphase. B. Cohesins are required to make the chromosomes more compact and thus to prevent tangling between different chromosomes. C. The mitotic spindle is composed of actin filaments and myosin filaments. D. Microtubule-dependent motor proteins and microtubule polymerization and depolymerization are mainly responsible for the organized movements of chromosomes during mitosis. E. The centromere nucleates a radial array of microtubules called an aster, and its duplication is triggered by S-Cdk. F. Each centrosome contains a pair of centrioles and hundreds of γ -tubulin rings that nucleate the growth of microtubules. 18-35 The cytoskeleton of an animal cell changes markedly between G 1 and early M phase (prophase) of the cell cycle. For each of the following sentences, choose one of the options enclosed in square brackets that best describes the changes to the cytoskeleton and its components.
Before mitosis, the number of centrosomes must [increase/decrease]. At the beginning of [anaphase/prophase] in animal cells, the centrosomes separate in a process driven partly by interactions between the [plus/minus] ends of microtubules arising
from the two centrosomes. Centrosome separation initiates the assembly of the bipolar mitotic spindle and is associated with a sudden [increase/decrease] in the dynamic instability of microtubules. In comparison with an interphase microtubule array, a mitotic aster contains a [smaller/larger] number of [longer/shorter] microtubules. Extracts from M-phase cells exhibit [increased/decreased/unchanged] rates of microtubule polymerization and increased frequencies of microtubule [shrinkage/growth]. The changes in microtubule dynamics are largely due to [enhanced/reduced] activity of microtubuleassociated proteins and [increased/decreased] activity of catastrophins. The new balance between polymerization and depolymerization of microtubules is necessary for the mitotic spindle to move the [replicated chromosomes/daughter chromosomes] to the metaphase plate. 18-36 Match each of the main classes of spindle microtubules from list 1 with their functions and features from list 2.
18-37 Disassembly of the nuclear envelope ________________. (a) causes the inner nuclear membrane to separate from the outer nuclear membrane (b) results in the conversion of the nuclear envelope into protein-free membrane vesicles (c) is triggered by the phosphorylation of integrins (d) must occur for kinetochore microtubules to form in animal cells 18-38 Consider an animal cell that has eight chromosomes (four pairs of homologous chromosomes) in G 1 phase. How many of each of the following structures will the cell have at mitotic prophase? A. sister chromatids B. centromeres C. kinetochores D. centrosomes E. centrioles
18-39 Which of the following statements about kinetochores is true? (a) Kinetochores assemble onto chromosomes during late prophase. (b) Kinetochores contain DNA-binding proteins that recognize sequences at the telomere of the chromosome. (c) Kinetochore proteins bind to the tubulin molecules at the minus end of microtubules. (d) Kinetochores assemble on chromosomes that lack centromeres. 18-40 Is the following statement true or false?
After the nuclear envelope breaks down, microtubules gain access to the chromosomes and, every so often, a randomly probing microtubule captures a chromosome and ultimately connects to the kinetochore to become a kinetochore microtubule of the spindle. 18-41 A friend declares that chromosomes are held at the metaphase plate by microtubules that push on each chromosome from opposite sides. Which of the following observations does not support your belief that the microtubules are pulling on the chromosomes? (a) the jiggling movement of chromosomes at the metaphase plate (b) the way in which chromosomes behave when the attachment between sister chromatids is severed (c) the way in which chromosomes behave when the attachment to one kinetochore is severed (d) the shape of chromosomes as they move toward the spindle poles at anaphase 18-42 Why should it be that drugs such as colchicine that inhibit microtubule polymerization and drugs such as Taxol that stabilize microtubules both inhibit mitosis? 18-43 Which of the following statements about the anaphase-promoting complex (APC) is false? (a) It promotes the degradation of proteins that regulate M phase. (b) It inhibits M-Cdk activity. (c) It is continuously active throughout the cell cycle. (d) M-Cdk stimulates its activity. 18-44 Which of the following statements is true? (a) Anaphase A must be completed before anaphase B can take place. (b) In cells in which anaphase B predominates, the spindle will elongate much less than in cells in which anaphase A dominates. (c) In anaphase A, both kinetochore and interpolar microtubules shorten. (d) In anaphase B, microtubules associated with the cell cortex shorten.
18-45 When introduced into mitotic cells, which of the following is expected to impair anaphase B but not anaphase A? (a) an antibody against myosin (b) ATPγ S, a nonhydrolyzable ATP analog that binds to and inhibits ATPases (c) an antibody against the motor proteins that move from the plus end of microtubules to the minus end (d) an antibody against the motor proteins that move from the minus end of microtubules toward the plus end 18-46 Which of the following precede the re-formation of the nuclear envelope during M phase in animal cells? (a) assembly of the contractile ring (b) decondensation of chromosomes (c) reassembly of the nuclear lamina (d) transcription of nuclear genes 18-47 A cell with nuclear lamins that cannot be phosphorylated in M phase will be unable to ________________. (a) reassemble its nuclear envelope at telophase (b) disassemble its nuclear lamina at prometaphase (c) begin to assemble a mitotic spindle (d) condense its chromosomes at prophase 18-48 The lengths of microtubules in various stages of mitosis depend on the balance between the activities of catastrophins, which destabilize microtubules, and microtubule-associated proteins (MAPs), which stabilize them. If you created cells with an increased number of catastrophin molecules, do you predict the length of the mitotic spindle will be longer, shorter, or unchanged, relative to the corresponding stage of mitosis in wild-type cells? What do you predict for a cell with increased numbers of MAPs? Explain your reasoning. 18-49 You have discovered a new protein that regulates microtubule dynamics. First, you isolated proteins from a cellular extract that bound to a tubulin affinity column. You then separated the proteins from each other by loading the mixture of proteins on an ion-exchange column, eluting the column with increasing salt concentration and collecting small “fractions” of protein as they dripped from the column. To test whether each fraction contained microtubule regulators, you mixed it with fluorescent tubulin and purified centrosomes, and then analyzed the reaction microscopically to measure the size of the aster microtubules formed. You found that fractions 8, 9, and 10 promoted the formation of unusually long aster microtubules. Because electrophoretic separation of the fractions on a gel revealed a plentiful protein with an apparent molecular weight of 98 kD, you named the protein p98.
A. B.
C.
D.
Does p98 behave like a MAP or a catastrophin? Propose two ways in which p98 might change the dynamic behavior of microtubules to account for the observed change in microtubule length. Hint: There are four simple possible mechanisms. Video microscopy of fluorescent tubulin in reactions with purified centrosomes allowed you to follow the behavior of individual microtubules over time. You graphed the changes in microtubule length in the absence (Figure Q18-51A) and presence (Figure Q18-51B) of p98. Five representative microtubules are shown for each condition. Does p98 alter the rate of microtubule growth or shrinkage? Does p98 alter the frequency of catastrophes (a sudden and rapid decline in microtubule length) or rescues (when a microtubule switches from shrinking to growing)? Explain your answers. After demonstrating the consequences of p98 on microtubule dynamics in vitro with the use of purified components, you want to determine whether the protein has the same effects in a complex cellular extract that naturally contains p98. Briefly describe an experiment that will allow you to determine what p98 normally does in mitotic extracts.
Figure Q18-51
C#'inesis 18-50 Cytokinesis in animal cells ________________. (a) requires ATP
(b) (c) (d)
leaves a small circular ‘scar’ of actin filaments on the inner surface of the plasma membrane is often followed by phosphorylation of integrins in the plasma membrane is assisted by motor proteins that pull on microtubules attached to the cell cortex
18-51 Which of the following statements is false? (a) The cleavage furrow is a puckering of the plasma membrane caused by the constriction of a ring of filaments attached to the plasma membrane. (b) The cleavage furrow will not begin to form in the absence of a mitotic spindle. (c) The cleavage furrow always forms perpendicular to the interpolar microtubules. (d) The cleavage furrow always forms in the middle of the cell. 18-52 Which of the following statements is false? (a) Cytokinesis in plant cells is mediated by the microtubule cytoskeleton. (b) Small membrane vesicles derived from the Golgi apparatus deliver new cell wall material for the new wall of the dividing cell. (c) The phragmoplast forms from the remains of interpolar microtubules of the mitotic spindle. (d) Motor proteins walking along the cytoskeleton are important for the contractile ring that guides formation of the new cell wall. 18-53 Which organelle fragments during mitosis? (a) endoplasmic reticulum (b) Golgi apparatus (c) mitochondrion (d) chloroplast
C'n#r'l '/ Cell Nu$ber and Cell Si3e 18-54 Programmed cell death occurs ________________. (a) by means of an intracellular suicide program (b) rarely and selectively only during animal development (c) only in unhealthy or abnormal cells (d) only during embryonic development 18-55 Apoptosis differs from necrosis in that necrosis ________________. (a) requires the reception of an extracellular signal (b) causes DNA to fragment (c) causes cells to swell and burst, whereas apoptotic cells shrink and condense (d) involves a caspase cascade
18-56 Which of the following statements about apoptosis is true? (a) Cells that constitutively express Bcl2 will be more prone to undergo apoptosis. (b) The prodomain of procaspases contains the catalytic activity necessary for procaspase activation. (c) Bax and Bak promote apoptosis by binding to procaspases in the apoptosome. (d) Apoptosis is promoted by the release of cytochrome c into the cytosol from mitochondria. 18-57 Imagine that you could microinject cytochrome c into the cytosol of both wildtype cells and cells that were lacking both Bax and Bak, which are apoptosispromoting members of the Bcl-2 family of proteins. Would you expect one, both, or neither of the cell lines to undergo apoptosis? Explain your reasoning. 18-58 The number of cells in an adult tissue or animal depends on cell proliferation. What else does it depend on? 18-59 What is the cause of the massive amount of programmed cell death of nerve cells (neurons) that occurs in the developing vertebrate nervous system, and what purpose does it serve? 18-60 For each of the following sentences, fill in the blanks with the best word or phrase selected from the list below. Not all words or phrases will be used; each word or phrase should be used only once.
The survival, __________________, and size of each cell in an animal are controlled by extracellular signal molecules secreted by neighboring and distant cells. Many of these signal molecules bind to a cell-surface __________________ and trigger various intracellular signaling pathways. One class of signal molecules, called __________________, stimulates cell division by releasing the molecular brakes that keep cells in the __________________ or __________________ phase of the cell cycle. Members of a second class of signal molecules are called __________________, because they stimulate cell growth and an increase in cell mass. The third class of signal molecules, called __________________, inhibits __________________ by regulating members of the __________________ family of proteins. In addition to such stimulatory factors, some signal proteins such as __________________ act negatively on other cells, inhibiting their survival, growth, or proliferation.
anaphase annihilation apoptosis arrestase Bcl-2 biosynthetic cascades caspase Cdk cyclin
differentiation G0 G1 G2 growth factors interphase ligand M mitogens
myostatin nourishment nutrition phosphatases proliferation receptor S survival factors transcription
18-61 Of the following mutations, which are likely to cause cell-cycle arrest? If you predict a cell-cycle arrest, indicate whether the cell will arrest in early G 1, late G1, or G2. Explain your answers. A. a mutation in a gene encoding a cell-surface mitogen receptor that makes the receptor active even in the absence of the mitogen B. a mutation that destroyed the kinase activity of S-Cdk C. a mutation that allowed G 1-Cdk to be active independently of its phosphorylation status D. a mutation that removed the phosphorylation sites on the Rb protein E. a mutation that inhibited the activity of Rb
CHAPTER 19 SE4 AN, GENET"CS © 2009
Garland Science Publisin!
Te 5ene/i#s '/ Se6 19-1
Organisms that reproduce sexually ________________________. (a) must be haploid, unlike organisms that reproduce asexually (b) can reproduce only with a partner that carries the same alleles
(c) (d)
create zygotes that are genetically identical to each other undergo a sexual reproductive cycle that involves an alternation of haploid cells with the generation of diploid cells
19-2
Which of the following statements is true? (a) Another name for the fertilized egg cell is the zygote. (b) Diploid organisms reproduce only sexually. (c) All sexually reproducing organisms must have two copies of every chromosome. (d) Gametes have only one chromosome.
19-3
Which of the following statements is false? (a) Asexual reproduction typically gives rise to offspring that are genetically identical. (b) Mutations in somatic cells are passed on to individuals of the next generation. (c) Sexual reproduction allows for a wide variety of gene combinations. (d) Gametes are specialized sex cells.
19-4
Somatic cells ___________________________. (a) are not necessary for sexual reproduction in all eucaryotic organisms (b) are used to produce germ line cells when organisms reach sexual maturity (c) leave no progeny (d) do not contain sex chromosomes
19-5
Which of the following statements about the benefits of sexual reproduction is false? (a) Sexual reproduction permits enhanced survival because the gametes that carry alleles enhancing survival in harsh environments are used preferentially during fertilization. (b) Unicellular organisms that can undergo sexual reproduction have an increased ability to adapt to harsh environments. (c) Sexual reproduction reshuffles genes, which is thought to help species survive in novel or varying environments. (d) Sexual reproduction can speed the elimination of deleterious alleles.
19-6
For each of the following sentences, fill in the blanks with the best word or phrase selected from the list below. Not all words or phrases will be used; each word or phrase may be used more than once. To reproduce sexually, an organism must create haploid __________________ cells, or __________________, from diploid cells via a specialized cell division called __________________. During mating, the father’s haploid cells,
called __________________ in animals, fuse with the mother’s haploid cells, called __________________. Cell fusion produces a diploid cell called a __________________, which undergoes many rounds of cell division to create the entire body of the new individual. The cells produced from the initial fusion event include __________________ cells that form most of the tissues of the body as well as the __________________-line cells that give rise to the next generation of progeny. allele bivalent eggs gametes
germ meiosis mitosis pedigree
pollen somatic sperm zygote
19-7
Why is sexual reproduction more beneficial to a species living in an unpredictable environment than to one living in a constant environment?
19-8
Is the following statement true or false? Explain. Somatic cells leave no progeny and thus, in an evolutionary sense, exist only to help create, sustain, and propagate the germ cells.
19-9
Sexual reproduction is a large drain on the limited resources of an individual. Nonetheless, sexual reproduction is common. In fact, to allow sexual reproduction, organisms have evolved many elaborate anatomical structures, cellular processes, and chemical signals. For example, flowers exist entirely to further the goal of sexual reproduction, and many plants have enlisted the help of bees and birds to aid in the dissemination of their germ cells. Describe one reason why most multicellular organisms have evolved to reproduce sexually instead of relying solely on asexual reproduction.
&ei'sis and %er#ili3a#i'n 19-10 Indicate whether each of the following is true for meiosis, mitosis, both, or neither. A. formation of a bivalent B. genetically identical products C. condensation of chromosomes D. segregation of all paternal chromosomes to one cell E. involvement of DNA replication 19-11 Meiosis is a highly specialized cell division in which several events occur in a precisely defined order. Please order the meiotic events listed below. 1. loss of cohesins near centromeres
2. 3. 4. 5. 6. 7. 8.
chromatid pairing chromosome condensation chromosome replication degradation of cohesins bound to chromosome arms formation of chiasmata (chiasmata = plural of chiasma) homolog pairing alignment of chromosomes at the metaphase plate
19-12 For each of the following sentences, choose one of the options enclosed in square brackets to make a correct statement.
Starting with a single diploid cell, mitosis produces [two/four] [identical/different] [haploid/diploid] cells, whereas meiosis yields [two/four] [identical/different] [haploid/diploid] cells. This is accomplished in meiosis because a single round of chromosome [replication/segregation] is followed by two sequential rounds of [replication/segregation]. Mitosis is more like meiosis [I/II] than meiosis [I/II]. In meiosis I, the kinetochores on sister chromatids behave [independently/coordinately] and thus attach to microtubules from the [same/opposite] spindle. The cohesinmediated glue between [chromatids/homologs] is regulated differently near the centromeres than along the chromosome arms. Cohesion is lost first at the [centromeres/arms] to allow segregation of [chromatids/homologs] and is lost later at the [centromeres/arms] to trigger segregation of [chromatids/homologs]. 19-13 In the absence of recombination, how many genetically different types of gamete can an organism with five homologous chromosome pairs produce? (a) 5 (b) 10 (c) 32 (d) 64 19-14 Which of the following statements most correctly describes meiosis? (a) Meiosis involves two rounds of DNA replication followed by a single cell division. (b) Meiosis involves a single round of DNA replication followed by four successive cell divisions. (c) Meiosis involves four rounds of DNA replication followed by two successive cell divisions. (d) Meiosis involves a single round of DNA replication followed by two successive cell divisions.
19-15 A diploid cell containing 32 chromosomes will make a haploid cell containing ___ chromosomes. (a) 8 (b) 16 (c) 30 (d) 64 19-16 Imagine a diploid sexually reproducing organism, Diploidus sexualis, that contains three pairs of chromosomes. This organism is unusual in that no recombination between homologous chromosomes occurs during meiosis. A. Assuming that the chromosomes are distributed independently during meiosis, how many different types of sperm or egg cells can a single individual of this species produce? B. What is the likelihood that two siblings of this species will be genetically identical? You can assume that the homologous chromosomes of each parent are different from one another and from their counterparts in the other parent. 19-17 You have received exactly half of your genetic material from your mother, who received exactly half of her genetic material from her mother (your grandmother). A. Explain why it is unlikely that you share exactly one-quarter of your genetic material with your grandmother, and instead it is more accurate to say that in general people receive an average of one-quarter of their genetic endowment from each grandparent. B. Consider a gene on chromosome 3 that you received from your grandmother. Is it likely you received an entire chromosome 3 from your grandmother? Why or why not? C. What portion of your genetic material do you share with your sibling? Your aunt? Your cousin? 19-18 You examine a worm that has two genders: males that produce sperm and hermaphrodites that produce both sperm and eggs. The diploid adult has four homologous pairs of chromosomes that undergo very little recombination. Given a choice, the hermaphrodites prefer to mate with males, but just to annoy the worm, you pluck a hermaphrodite out of the wild and fertilize its eggs with its own sperm. Assuming that all the resulting offspring are viable, what fraction do you expect to be genetically identical to the parent worm? Assume that each chromosome in the original hermaphrodite is genetically distinct from its homolog. (a) All (b) None (c) 1/16 (d) 1/256
19-19 Which of the following statements about meiosis is true? (a) During meiosis, the paternal chromosomes pair with the maternal chromosomes before lining up at the metaphase plate. (b) Unicellular organisms that have a haploid state undergo meiosis instead of mitosis during cell division. (c) Meiosis produces four genetically identical cells. (d) In general, meiosis is faster than mitosis. 19-20 Figure Q19-20 is a diagram of chromosomes during meiosis.
Figure Q19-20 A.
B.
On the diagram, indicate which label lines correspond to the following items: (1) sister chromatids, (2) homologous chromosomes, (3) bivalent, (4) chiasma. On the figure, draw as small circles (oooo) the cohesin “glue” that is released in meiotic division I, and draw as small crosses (xxxx) the cohesin glue that is released in meiotic division II.
19-21 During recombination ________________________. (a) sister chromatids undergo crossing-over with each other (b) chiasmata hold chromosomes together (c) one crossover event occurs for each pair of human chromosomes (d) the synaptonemal complex keeps the sister chromatids together until anaphase II 19-22 After the first meiotic cell division ________________________. (a) two haploid gametes are produced
(b) (c) (d)
cells are produced that contain the same number of chromosomes as somatic cells the number of chromosomes will vary depending on how the paternal and maternal chromosomes align at the metaphase plate DNA replication occurs
19-23 Meiosis includes a recombination checkpoint that is analogous to the checkpoints in cell cycle progression. Double-stranded breaks in the DNA initiate recombination in meiosis. The broken end of a DNA molecule finds the corresponding sequence on a homologous chromosome and exchanges a chromosomal segment with its homolog, thereby repairing the break. Ongoing recombination sends a negative regulatory signal that prevents cells from entering meiotic division I. A. Mutations in several genes inactivate the recombination checkpoint. What do you predict will happen if a cell proceeds through meiotic division I before completing recombination? B. What will happen if a cell fails to initiate recombination and proceeds through meiotic division I? Meiotic division II? 19-24 In some fungi, cell division during meiosis gives rise to an ordered spore sac containing a row of four haploid spores, as shown in Figure Q19-24A. The position of each spore within the sac reflects its relation to its neighbors; in other words, spores that result from the same meiosis II division are positioned next to each other. You notice that a strain of the fungus produced by crossing a darkcolored strain with a light-colored strain gives rise mostly to spore sacs as shown in Figure Q19-24B, with a few spore sacs like those in Figure Q19-24C. Indicate whether the following statements are correct. Explain your reasoning.
Figure Q19-24
A. B. C. D. E.
Meiosis I and meiosis II in the fungus occur in the reverse order from that which occurs in humans. Recombination in the fungus can occur during prophase I. Recombination in the fungus cannot occur during prophase II. The spore sacs in panel C result from recombination between the centromere and the gene responsible for spore color. Recombination has occurred between the gene responsible for spore color and the end of the chromosome arm.
19-25 In mammals, there are two sex chromosomes, X and Y, which behave like homologous chromosomes during meiosis. Normal males have one X chromosome and one Y chromosome, and normal females have two X chromosomes. Males with an extra Y chromosome (XYY) are found occasionally. Which of the following could give rise to such an XYY male? Explain your answer. (a) nondisjunction in the first meiotic division of spermatogenesis; normal meiosis in the mother (b) nondisjunction in the second meiotic division of spermatogenesis; normal meiosis in the mother (c) nondisjunction in the first meiotic division of oogenesis; normal meiosis in the father (d) nondisjunction in the second meiotic division of oogenesis; normal meiosis in the father 19-26 Which of the following would not lead to aneuploidy during meiosis? (a) sister chromatids segregating inappropriately (b) non-sister chromatids segregating inappropriately (c) a reciprocal rearrangement of parts between nonhomologous chromosomes (e.g., the left arm of chromosome 2 exchanging places with the right arm of chromosome 3) (d) an extra set of chromosomes produced during S phase (e.g., if paternal chromosome 3 were replicated twice) 19-27 A single nondisjunction event during meiosis ___________________. (a) will block recombination (b) will occur only during meiosis II (c) cannot occur with sex chromosomes (d) will involve the production of two normal gametes if it occurs during meiosis II 19-28 During fertilization in humans, _______________________. (a) a wave of Ca2+ ions is released in the fertilized egg’s cytoplasm (b) only one sperm binds to the unfertilized egg
(c) (d)
a sperm moves in a random fashion until it encounters an egg several sperm pronuclei compete in the cytoplasm to fuse with the egg nucleus
19-29 Do you agree or disagree with the following statement? Explain your answer.
If a diploid organism has 16 chromosomes (and thus 8 pairs of homologous chromosomes), that organism can produce only 2 8 genetically different gametes.
&endel and #e La(s '/ "neri#ance 19-30 Which of the following statements about Mendel’s experiments is false? (a) The pea plants could undergo both cross-fertilization and self-fertilization. (b) The true-breeding strains were homozygous for the traits that Mendel examined. (c) The egg can carry either the allele from the maternal or the paternal chromosome. (d) All traits that Mendel studied were recessive. Questions 19-31 to 19-34 use the following information and Figure Q19-31. These questions may be used independently, or as a group.
Figure Q19-31 diagrams one of Mendel’s experiments using the round and wrinkled seed traits.
Figure Q19-31 19-31 Which of the following could be considered a true-breeding strain for the seed shape phenotype? (See Figure Q19-31.) (a) all of the round-seeded plants produced in the F 2 generation (b) all of the wrinkle-seeded plants produced in the F 2 generation (c) all of the round-seeded plants produced in the F 1 generation (d) half of the round-seeded plants produced in the F 2 generation 19-32 If you crossed the round-seeded plants obtained in the F 1 generation with a truebreeding strain of round-seeded plants, how many wrinkle-seeded plants would you expect to obtain in the next generation? (See Figure Q19-31.) (a) none (b) 25% (c) 75% (d) all 19-33 If you crossed the round-seeded plants obtained in the F 1 generation with a truebreeding strain of wrinkle-seeded plants, how many round-seeded plants would you expect to obtain in the next generation? (See Figure Q19-31.) (a) 25% (b) 50% (c) 75% (d) 100% 19-34 Which of the following statements about the round-seeded pea plants obtained in the F2 generation is false? (See Figure Q19-31.) (a) These plants are phenotypically identical for seed shape. (b) Two-thirds of these plants are expected to be heterozygous for the seed shape allele. (c) We expect 25% of these plants to be homozygous for the seed shape allele. (d) If these plants were crossed to wrinkle-seeded plants, some of these plants would produce only round-seeded plants. 19-35 Which of the following reasons was essential for Mendel to disprove the theory of blended inheritance? (a) The traits that Mendel examined all involved genes that did not display linkage. (b) The traits that Mendel examined all involved the reproductive structures of the pea plant. (c) Mendel pioneered techniques permitting the fusion of male and female gametes from the same plant to produce a zygote.
(d)
The traits that Mendel examined involved an allele that was dominant and an allele that was recessive.
19-36 Which of the following reasons was essential for Mendel’s law of independent assortment? (a) All the traits that Mendel examined involved genes that did not display linkage. (b) Several of the phenotypes that Mendel examined involved color. (c) Mendel observed chromosomal segregation in pea plant cells. (d) Mendel carried out his experiments on plants and not on fungi. 19-37 Is the following statement true or false? Explain.
The phenotype of an organism reflects all of the alleles carried by that individual. 19-38 With respect to gene E on the chromosome drawn in Figure Q19-38, which gene is least likely to behave according to Mendel’s law of independent assortment? Explain your answer.
Figure Q19-38 19-39 Cystic fibrosis results from mutations in a single gene that lies on chromosome 7. Only homozygous mutant ( ff ) individuals are sick; homozygous wild-type ( FF ) and heterozygous ( Ff ) individuals are healthy. A healthy married couple has one child with cystic fibrosis and the wife is pregnant with a second child. A. What is the genotype of the mother? The father? B. What is the chance that the second child will have cystic fibrosis? 19-40 Sickle-cell anemia is caused by a mutant allele of a hemoglobin gene. Individuals with two mutant alleles have sickle-cell anemia. Individuals homozygous and
heterozygous for the mutant gene are more resistant to malaria than those with two wild-type alleles. Is this mutation dominant, recessive, or co-dominant? 19-41 Your friend has obtained some pea seeds from the Abbey of St. Thomas in Brno, where Gregor Mendel worked. He is very excited because not only did he obtain some yellow and green pea seeds from true-breeding plants (like the ones used in Mendel’s famous experiment), he was also able to obtain some purple pea seeds from a true-breeding plant. First, your friend takes the true-breeding yellow and green pea seeds, repeats the cross that Gregor Mendel did, and obtains the same results: he sees 100% yellow-seeded pea plants in the F 1 generation, and 75% yellow-seeded pea plants and 25% green-seeded pea plants in the F 2 generation. His results are illustrated in Figure Q19-41A. Your friend then decides to set up two more crosses. For cross #2, he crosses the true-breeding purple-seeded pea plants to the true-breeding yellow-seeded pea plants. The results from this cross are shown in Figure Q19-41B. Next, for cross #3, he crosses the true-breeding purple-seeded pea plants to the true-breeding green-seeded pea plants. These results are shown in Figure Q19-41C.
Figure Q19-41 Given these results, if you were to take the purple-seeded pea plants produced in the F1 generation in cross #2 and cross them to the purple-seeded pea plants produced in the F 1 generation of cross #3, what do you expect that the phenotype of the progeny would look like? Explain your answer. 19-42 You are given two true-breeding strains of hamster. One strain has white fur color and the other has a dark brown fur color. When you cross the white fur strain to the dark brown fur strain, you obtain F 1 progeny that have a light brown fur color. When you cross the F 1 progeny with each other, 25% of the F 2 generation have white fur, 25% have dark brown fur, and 50% have light brown fur. How many genes crucial for fur coloration differ between the two starting strains? Explain your answer. Extra credit: Propose a molecular mechanism for how fur color is determined in this species of hamster. 19-43 Loss-of-function mutations ________________________. (a) cause the production of proteins that are active in inappropriate circumstances (b) will usually show a phenotype when heterozygous (c) are only present in a population at barely detectable levels (d) are usually recessive
Gene#ics as an E6eri$en#al T''l 19-44 Conditional alleles are mutant gene versions encoding proteins that can function normally at the permissive condition but are defective at the restrictive condition. One commonly used condition is temperature. Conditional alleles are especially useful to geneticists because they permit the study of essential genes. At the permissive temperature, the organism lives normally. When the organism is shifted to the non-permissive temperature, the effect of inactivating the gene can be studied. Which of the three types of mutation shown in Figure Q19-44 is most likely to lead to a conditional allele? Explain your answer.
Figure Q19-44 19-45 You performed a genetic screen in C. elegans and found two mutations (#1 and #2) that cause antisocial behavior. You want to learn whether these are mutations in the same gene or different genes, so you cross mutant #1 and mutant #2 together to perform a complementation test. Imagine that the mutations are in
different genes: mutation #1 is in gene M and mutation #2 in gene N .
Figure Q19-45 A.
B.
C. D.
What is the outcome of a complementation test if #1 and #2 are both recessive mutations ( m and n, respectively)? Fill in the empty oval in Figure Q19-45A and indicate whether the offspring exhibits social or antisocial behavior. What is the outcome if #1 is dominant and #2 is recessive ( M * and n)? Fill in the empty oval in Figure Q19-45B and indicate whether the offspring exhibits social or antisocial behavior. For the case in A, would the phenotype of the offspring differ if the two mutations were in the same gene? For the case in B, would the phenotype of the offspring differ if the two mutations were in the same gene? Are complementation tests useful for analyzing dominant mutations?
19-46 Do you agree or disagree with the following statement? Explain your answer.
A trait that is found at a low frequency in the population has to be a recessive trait. 19-47 You are studying a diploid yeast strain that normally uses glucose as an energy source but can use maltose when no glucose is present. You are interested in understanding how this yeast strain metabolizes maltose as an alternative energy source. You isolate the genes involved in maltose metabolism by screening for yeast that cannot grow when maltose is the sole energy source. You find six different mutants, all of which are recessive, and name these alleles mal1, mal2, mal3, mal4, mal5, and mal6 . Next, you isolate gametes from the homozygous diploid mutant yeast strains and perform crosses between the different strains to do complementation analysis, because you wish to determine whether the mutations are likely to affect the same or different genes. Your results are shown in Table Q19-47.
Table Q19-47 Complementation analysis of mal genes. In how many genes are you likely to have isolated mutations? Which alleles seem to affect the same genes? Explain your answer. 19-48 Gene A is located near gene B on chromosome 13 in humans. A mutation in the germ line of an individual with the haplotype AB generates gametes with the genotype Ab. Many descendents of this founder individual carry the b mutation, which predisposes carriers to high blood pressure. Initially, all descendents who inherit the b mutation also inherit the neighboring A allele. Through the generations, fewer and fewer descendents with the b mutation carry the A allele, and instead they have the a allele. (Individuals with A and a are equally healthy and fit.) Explain how the b and A alleles are separated. 19-49 Shown in Figure Q19-49 is a genetic pedigree of a family with several members affected by a heritable disease. Affected individuals are shown in black and healthy individuals are shown in white. Males are shown as boxes and females as circles. Can a single mutation explain the pattern of inheritance? Is the mutation responsible for the disease dominant or recessive? Is the mutation carried on the X chromosome, the Y chromosome, or an autosome?
Figure Q19-49 19-50 The single nucleotide polymorphisms found in the human population __________________. (a) are important for genetic mapping because they represent mutations in genes important for human disease (b) are rarely found among blood relatives (c) can be linked into haplotype blocks (d) arose mainly during the past 10,000 years
H'( )e Kn'(* 8sin! SNPs #' Ge# a Handle 'n Hu$an ,isease 19-51 You are trying to map a human gene thought to be involved in cat allergies. Because you know this gene is on chromosome 20, you decide to examine the linkage of several SNPs located on chromosome 20 with respect to the gene involved in cat allergies. You have
obtained DNA from 10 individuals, and you know whether they are allergic to cats. Your SNP results are shown in Table Q19-51.
Table Q19-51 SNP tests for chromosome 20. (+ indicates the presence of SNP.) A. B.
Which SNP is most likely to be tightly linked to the gene involved in cat allergies? Explain your answer. Of the SNPs tested above, which is likely to be the next closest to the gene responsible for the allergic state? Why?
19-52 Any two human beings typically have an estimated 0.1% difference in their nucleotide sequences, which is equivalent to about 3 million nucleotide differences. These differences are the basis of the SNPs used to construct genetic linkage maps. Some of these SNPs actually lie in the region of the DNA that codes for the protein, yet they have no effect on the phenotype of individuals carrying the SNP on both homologous chromosomes. Explain how some SNPs can lie within the portion of the DNA that codes for the protein and yet have no discernible effect on the protein’s activity. 19-53 Finding co-inheritance of a SNP variant and a disease tells scientists that ____________________. (a) everybody who carries this SNP will get the disease (b) sequences within the SNP cause the disease (c) a gene important for causing the disease is linked to the SNP (d) SNPs on other chromosomes will not be co-inherited with the disease 19-54 You decide to carry out genetic association studies and identify a SNP variant that is found significantly more often in individuals who have schizophrenia than in those who are not affected. This SNP is found within an intron of the SZP gene. A. Can you deduce that an abnormality of the SZP gene is a cause of increased risk of schizophrenia? B. Can you say whether the SNP variant itself is a cause?
CHAPTER 20 CELL8LAR CO&&8N"T"ES* T"SS8ES STE& CELLS AN, CANCER © 2009
Garland Science Publisin!
E6#racellular &a#ri6 and C'nnec#i.e Tissues 20-1
Both multicellular plants and animals have _____________________. (a) cells capable of locomotion (b) cells with cell walls (c) a cytoskeleton composed of actin filaments, microtubules, and intermediate filaments (d) tissues composed of multiple different cell types
20-2
For each of the following sentences, fill in the blanks with the best word or phrase selected from the list below. Not all words or phrases will be used; use each word or phrase only once. Plants are sedentary and thus their cells have different needs from those of cells found in motile animals. For example, in plant cells, __________________ generates the turgor pressure that drives cell growth. Plants have cell walls, but cell growth is possible in the developing tissue because the __________________ cell walls are expandable. The __________________ cell walls are deposited once growth has stopped, and can be specially adapted to their function. Fibers made from __________________ (the most abundant organic macromolecule on Earth) are found in plant cell walls, and provide tensile strength. In woody tissues, the __________________ in the cell walls makes the tissue more rigid and waterproof. The deposition of the cell wall is directed by the __________________ cytoskeleton. cellulose collagen epidermis nuclear pectin
20-3
lignin membranous osmosis lamin primary
secondary microtubule tertiary actin
Which of the following statements about plant cell walls is true? (a) The microtubule cytoskeleton directs the orientation in which cellulose is deposited in the cell wall.
(b) (c) (d)
20-4
The molecular components of the cell wall are the same in all plant tissues. Because plant cell walls are rigid, they are not deposited until the cell has stopped growing. The cellulose found in cell walls is produced as a precursor molecule in the cell and delivered to the extracellular space by exocytosis.
Indicate the direction in which the plant cell shown in Figure Q20-4 is most likely to grow. The black lines indicate the direction of the cellulose microfibrils around the cell. Explain your answer.
Figure Q20-4 20-5
Which of the following molecules are not found in plants? (a) cellulose (b) lignin (c) collagen (d) pectin
20-6
Indicate whether the following molecules are found in plants, animals, or both. A. intermediate filaments B. cell walls C. microtubules D. cellulose E. collagen
20-7
Which of the following statements about animal connective tissues is true? (a) Enzymes embedded in the plasma membrane synthesize the collagen in the extracellular matrix extracellularly. (b) In connective tissue, the intermediate filaments within the cells are important for carrying the mechanical load. (c) Cells can attach to a collagen matrix by using fibronectin, an integral membrane protein. (d) Proteoglycans can resist compression in the extracellular matrix.
20-8
A major distinction between the connective tissues in an animal and other main tissue types such as epithelium, nervous tissue, or muscle is _______________. (a) the ability of connective tissue cells such as fibroblasts to change shape (b) the amount of extracellular matrix in connective tissues (c) the ability of connective tissues to withstand mechanical stresses
(d)
20-9
the numerous connections that connective tissue cells make with each other
What are the main structures providing tensile strength in the following? A. animal connective tissue B. animal epidermis C. plant cell walls
20-10 Do you agree or disagree with the following statement? Explain your answer.
Like many other extracellular proteins, newly synthesized collagen molecules undergo post-translational processing inside the cell to convert them into their mature form; they are then secreted and self-assemble into fibrils in the extracellular space. 20-11 Fibroblasts organize the collagen of the extracellular matrix by ______________. (a) cutting and rejoining the fibrils (b) processing procollagen into collagen (c) twisting fibrils together to make ropelike fibers (d) pulling the collagen into sheets or cables after it has been secreted 20-12 Match the four lettered lines in Figure Q20-12 with the appropriate numbered label.
Figure Q20-12 1. integrin 2. actin 3. collagen 4. fibronectin
20-13 Which of the following statements about integrins is false? (a) Integrins use adaptor proteins to interact with the microtubule cytoskeleton. (b) Integrins can switch to an activated state by binding to an extracellular matrix molecule. (c) Integrins can switch to an activated state by binding to an intracellular protein. (d) An activated integrin molecule takes on an extended conformation. 20-14 Proteoglycans in the extracellular matrix of animal tissues ________________. (a) chiefly provide tensile strength (b) allow cartilage to resist compression (c) are linked to microtubules through the plasma membrane (d) are polysaccharides composed of glucose subunits 20-15 Which of the following statements is false? (a) Proteoglycans can act as filters to regulate which molecules pass through the extracellular medium. (b) The negative charge associated with proteoglycans attracts cations, which cause water to be sucked into the extracellular matrix. (c) Proteoglycans are a major component of compact connective tissues but are relatively unimportant in watery tissues such as the jellylike substance in the interior of the eye. (d) Glycosaminoglycans are components of proteoglycan.
Ei#elial See#s and Cell :unc#i'ns 20-16 For each of the following sentences, fill in the blanks with the best word or phrase selected from the list below. Not all words or phrases will be used; use each word or phrase only once.
__________________ join the intermediate filaments in one cell to those in the neighboring cell. __________________ anchor intermediate filaments in a cell to the extracellular matrix. __________________ involve cadherin connections between neighboring cells and are anchorage sites for actin filaments. __________________ permit the passage of small molecules from one cell to its adjacent cell. __________________ prevent the leakage of molecules between adjacent cells. adherens junctions desmosomes
gap junctions hemidesmosomes
highway junctions tight junctions
20-17 Label the five different types of cell–cell junction shown in Figure Q21-17, and identify the apical and basal surfaces of the epithelium.
Figure Q20-! 20-18 Match the molecules (list 1) with the cell structures in which they are involved (list 2). A cell structure may be listed more or less than once.
20-19 A basal lamina ______________________. (a) is a thin layer of connective tissue cells and matrix underlying an epithelium (b) is a thin layer of extracellular matrix underlying an epithelium (c) is attached to the apical surface of an epithelium (d) separates epithelial cells from each other 20-20 Tight junctions ______________________. (a) allow small water-soluble molecules to pass from cell to cell (b) interact with the intermediate filaments inside the cell
(c) (d)
are formed from claudins and occludins are found in cells in connective tissues
20-21 Adherens junctions ______________________. (a) can be used to bend epithelial sheets into tubes (b) are most often found at the basal surface of cells (c) are found only in adult tissues (d) involve fibronectin and integrin interactions 20-22 At desmosomes, cadherin molecules are connected to ________________. (a) actin filaments (b) intermediate filaments (c) microtubules (d) gap junctions 20-23 Hemidesmosomes are important for ______________________. (a) tubulation of epithelial sheets (b) linkages to glycosaminoglycans (c) forming the basal lamina (d) attaching epithelial cells to the extracellular matrix 20-24 Which of the following statements about gap junctions is false? (a) Gap junctions are made of connexons. (b) Molecules up to 1000 daltons in molecular weight can move across gap junctions. (c) Because gap junctions do not allow ions to pass through, they are not used for electrically coupling cells. (d) Gap junctions can close in response to extracellular signals. 20-25 Which type of junction involves a connection to the actin cytoskeleton? (a) adherens junctions (b) desmosomes (c) tight junctions (d) gap junctions 20-26 Which type of junction contributes the most to the polarization of epithelial cells? (a) adherens junctions (b) desmosomes (c) tight junctions (d) gap junctions 20-27 Cadherins ______________________. (a) are used to transfer proteins from one cell to another (b) mediate cell–cell attachments through homophilic interactions
(c) (d)
are abundant in the plant cell wall bind to collagen fibrils
20-28 Plasmodesmata ______________________. (a) permit small molecules to pass from one cell to another (b) are found only in animal cells (c) are closed by the neurotransmitter dopamine (d) provide tensile strength
Tissue &ain#enance and Rene(al 20-29 Match the appropriate cell type found in the mammalian skin with the best description of its function.
20-30 Name the three key mechanisms important for maintaining the organization of cells into tissues. 20-31 Place the following in order of their replacement times, from shortest to longest. ". epidermal cell #. nerve cell $. bone matrix %. red blood cell &. cell lining the gut 20-32 Cells that are terminally differentiated ______________________. (a) will undergo apoptosis within a few days (b) can no longer undergo cell division (c) are unable to move (d) no longer produce RNAs 20-33 An adult hemopoietic stem cell found in the bone marrow ______________________. (a) will occasionally produce epidermal cells when necessary (b) can produce only red blood cells (c) can undergo self-renewing divisions for the lifetime of a healthy animal (d) will express all the same transcription factors as those found in an unfertilized egg
20-34 Mouse embryonic stem (ES) cells ______________________. (a) can only be produced through therapeutic cloning (b) can give rise to all tissues and cell types in the body except germ cells (c) can be implanted in foster mothers to produce cloned cows and other animals (d) come from the inner cell mass of early embryos 20-35 How do reproductive cloning and therapeutic cloning differ? (a) The DNA in the nucleus of cells produced for therapeutic cloning is genetically identical to the donor genome, whereas in cells produced for reproductive cloning it is not. (b) Reproductive cloning requires a supply of fertilized donor egg cells, whereas therapeutic cloning requires unfertilized egg cells. (c) Therapeutic cloning requires nuclear transplantation, whereas reproductive cloning does not. (d) Embryos are placed into foster mothers during reproductive cloning but not during therapeutic cloning. 20-36 Induced pluripotent stem (iPS) cells ______________________. (a) are created by the expression of a set of key genes in cells derived from adult tissues so that these cells can differentiate into a variety of cell types (b) require a supply of donor egg cells, such as embryonic stem cells (c) can differentiate into a greater variety of adult tissues than embryonic stem cells (d) are created by nuclear transplantation 20-37 A stem cell divides into two daughter cells. One of the daughter cells goes on to become a terminally differentiated cell. What is the typical fate of the other daughter cell? 20-38 Your friend is a pioneer in ES cell research. In her research, she uses an ES cell line that originated from an inbred strain of laboratory mice called FG426. She has just figured out methods that allow her to grow an entire liver from an ES cell and has successfully grown 10 livers. She demonstrates that the newly grown livers are functional by successfully transplanting one of the new livers into a FG426 laboratory mouse.
You are particularly excited about this, because you have a sick pet mouse, Squeaky. You are very attached to Squeaky, as you found him when you were out camping in New Hampshire. Unfortunately, Squeaky has developed liver disease and will not live much longer without a liver transplant. After you see your friend on TV talking about her new method for growing mouse livers, you immediately grab your cell phone to ask her whether Squeaky could have one of the newly grown livers. Just as you are about to dial your friend, you remember something
you learned in cell biology and realize that instead, you should ask your friend about possibly using therapeutic cloning for Squeaky’s benefit. A. Why do you think that one of the newly grown livers may not work in Squeaky? B. Explain why therapeutic cloning would solve this problem.
Cancer 20-39 A malignant tumor is more dangerous than a benign tumor because ______________________. (a) its cells are proliferating faster (b) it causes neighboring cells to mutate (c) its cells attack and phagocytose neighboring normal tissue cells (d) its cells invade other tissues 20-40 Which of the following statements about cancer is false? (a) Viruses cause some cancers. (b) Tobacco use is responsible for more than 20% of all cancer deaths. (c) A mutation in even a single cancer-critical gene is sufficient to convert a normal cell into a cancer cell. (d) Chemical carcinogens cause cancer by changing the nucleotide sequence of DNA. 20-41 Cancer is a disease of enhanced proliferation and cell survival. DNA repair mechanisms are normally important for cell survival. 'hen a cell senses %(" damage) the cell cycle is inhibited until the damage is fixed. *iven the importance of %(" repair mechanisms) how can their failure can lead to the production of cancer cells with a competitive advantage over normal cells+ 20-42 Which of the following genetic changes cannot convert a proto-oncogene into an oncogene? (a) A mutation that introduces a stop codon immediately after the codon for the initiator methionine. (b) A mutation within the coding sequence that makes the protein hyperactive. (c) An amplification of the number of copies of the proto-oncogene, causing overproduction of the normal protein. (d) A mutation in the promoter of the proto-oncogene, causing the normal protein to be transcribed and translated at an abnormally high level. 20-43 Which of the following statements about tumor suppressor genes is false? (a) Gene amplification of a tumor suppressor gene is less dangerous than gene amplification of a proto-oncogene. (b) Cells with one functional copy of a tumor suppressor gene will usually proliferate faster than normal cells.
(c) (d)
Inactivation of tumor suppressor genes leads to enhanced cell survival and proliferation. Individuals with only one functional copy of a tumor suppressor gene are more prone to cancer than individuals with two functional copies of a tumor suppressor gene.
20-44 A certain mutation in the receptor for epidermal growth factor (EGF) causes the mutated receptor protein to send a positive signal along the associated intracellular signaling pathway even when the EGF ligand is not bound to it. This signal leads to abnormal cell proliferation in the absence of growth factor. On the basis of this information, would you class the gene for the EGF receptor as a tumor suppressor gene or a potential oncogene? Explain your answer. 20-45 Ras is a GTP-binding protein that is often defective in cancer cells. A signal from a growth factor through a receptor tyrosine kinase often stimulates normal cells to divide. When the receptor tyrosine kinase binds the growth factor, Ras is stimulated to bind GTP. Ras in turn activates proteins that promote cell proliferation. A common mutation in cancerous cells causes Ras to behave as though it were bound to GTP all the time. A. Why is this mutation advantageous to cancerous cells? B. Your friend decides that the signaling pathway involving the Ras protein is a good target for drug design, because the Ras protein is often defective in cancer cells. Your friend designs a drug that will turn off the receptor tyrosine kinase by preventing it from dimerizing. Do you think that this drug will affect cells that have a defective Ras protein that acts as if it were always bound to GTP? Why or why not? 20-46 People who inherit one copy of the Rb (retinoblastoma) gene that is normal and one copy that is mutated—that is, people who are heterozygous for Rb—have a greatly increased risk of cancer.
*iven this information) do you agree or disagree with the following statement+ &xplain your answer. The Rb mutation must have a dominant effect, which means that it must result in an increase in Rb function. Thus, Rb in its mutant form must be an oncogene. 20-47 Figure Q20-47 mutations that might development of Explain why the loss advantageous to
shows a sequence of underlie the colorectal cancer. of p53 is cancerous cells.
Figure Q20-,! 20-48 Drugs that block the function of oncogenic proteins hold great promise in the fight against cancer. Should cancer researchers also be attempting to design drugs that will interfere with the products of tumor suppressor genes? Explain. 20-49 Rb is a tumor suppressor gene; its normal function is to help restrain cell division. Loss of both copies of Rb is a causative factor in some kinds of cancer. You propose to treat these cancers by injecting the patients with a viral vector that carries a copy of the Rb gene and has the ability to infect all the cells of the body, thereby artificially driving expression of Rb in all the cells, including the cancer cells. Your colleague says “No!—You'll simply kill the patient, because you will halt cell division throughout the body.” A. Why would halting cell division throughout the body kill a full-grown adult person? B. Is your colleague right in thinking that forced expression of Rb in every cell will halt all cell division? 20-50 In 1971, Dr Judah Folkman published the “angiogenic hypothesis” suggesting that a tumor cannot grow beyond 1–2 millimeters without the development (angiogenesis) of new blood vessels that provide access to oxygen and nutrients. During the 1990s, it was discovered that vascular endothelial growth factor (VEGF) stimulates the proliferation and migration of the cells that form blood vessels, leading to the formation of new blood vessels. VEGF binds to receptor tyrosine kinases (RTKs) on the cell surface and causes the RTKs to dimerize and become active, thereby initiating an intracellular signaling cascade that stimulates cell division and inhibits apoptosis. Many cancer cells secrete high levels of VEGF. Increased VEGF expression in a tumor is correlated with a poor medical outcome for the patient. Some evidence suggests that blocking VEGF-dependent signaling may prevent the formation of new blood vessels and lead to the death of
