Molecular Cell Biology 7th edition Harvey Lodish, Arnold Berk, Chris A. Kaiser, Monty Krieger, Anthony Bretscher, Hidde Ploegh, Angelika Amon, Matthew P. Scott - Solutions

Disulfide bonds help to stabilize the three-dimensional structure of proteins. What amino acids are involved in the formation of disulfide bonds? Does the formation of a disulfide bond increase or decrease entropy (ΔS)?
Olfaction occurs when volatile compounds bind to specific odorant receptors. In mammals, each olfactory receptor neuron in the olfactory nasal epithelium expresses a single type of odorant receptor. These odorant receptors constitute a large multigene family (> 1000 members) of related proteins.
Compare the structures and functions of the receptor molecules for salty and sour taste; the taste receptor molecules for sweetness, bitterness, and umami; and odor-receptor molecules.
Compare and contrast electrical and chemical synapses.
What is the role of dynamin in recycling synaptic vesicles? What evidence supports this?
Researchers have isolated two E-cadherin mutant isoforms that are hypothesized to function differently from the isoform of the wild-type E-cadherin. An E-cadherin negative mammary carcinoma cell line was transfected with the mutant E-cadherin genes A (part a in the figure; triangles), or B (part b;
Compare plasmodesmata in plant cells to gap junctions in animal cells?
The structure of a plant cell wall needs to loosen to accommodate cell growth. What signaling molecule controls this process?
How do changes in molecular connections between the extracellular matrix (ECM) and cytoskeleton give rise to Duchenne muscular dystrophy?
How do changes in molecular connections between the extracellular matrix (ECM) and cytoskeleton give rise to Duchenne muscular dystrophy?
Blood clotting is a crucial function for mammalian survival. How do the multi-adhesive properties of fibronectin lead to the recruitment of platelets to blood clots?
Describe the major activity and possible localization of the three major subgroups of proteins that remodel/degrade the ECM in physiological or pathological tissue remodeling. Identify a pathological condition in which these proteins play a key role?
You have synthesized an oligopeptide containing an RGD sequence surrounded by other amino acids. What is the effect of this peptide when added to a fibroblast cell culture grown on a layer of fibronectin absorbed to the tissue culture dish? Why does this happen?
Many proteoglycans have cell-signaling roles. Regulation of feeding behavior by syndecans in the hypothalamic region of the brain is one example. How is this regulation accomplished?
Compare the functions and properties of each of three types of macromolecules that are abundant in the extracellular matrix of all tissues?
Explain how changes in integrin structure mediate outside in and inside-out signaling?
What is collagen, and how is it synthesized? How do we know that collagen is required for tissue integrity?
Gap junctions between heart muscle cells and gap junctions between uterine myometrial smooth muscle cells form a connection that provides for rapid communication. What is this called? How is uterine myometrial smooth-muscle-cell gap-junction communication up-regulated for parturition (childbirth)?
What is the normal function of tight junctions? What can happen to tissues when tight junctions do not function properly?
Together with their role in connecting the lateral membranes of adjacent epithelial cells, adherens junctions play a role in controlling cell shape. What associated intracellular structure and proteins are involved in this role?
Cadherins are known to mediate homophilic interactions between cells. What is a homophilic intetaction, and how can it be demonstrated experimentally for E-cadherins? What component of the extracellular environment is required for the homophilic interactions mediated by cadherins, and how can this
Describe the two phenomena that give rise to the diversity of adhesive molecules such as cadherins. What additional phenomenon gives rise to the diversity of integrins?
Cyclins are a required component of cyclin-CDK complexes for regulated progression through the eukaryotic cell cycle. Most cyclins are progressively synthesized and then degraded systematically in a temporal fashion at various points in the cell cycle. As we discussed in Chapter 7, cellular protein
Many of the proteins that regulate transit through the cell cycle have been characterized. Xnf7, identified in extracts of Xenopus eggs, binds to the anaphase-promoting complex/ cyclosome (A PC/C). To elucidate the function of this protein, studies have been undertaken in which Xnf7 either has been
Individuals with the hereditary disorder ataxia telangiectasia suffer from neurodegeneration, immunodeficiency, and increased incidence of cancer. The genetic basis for ataxia telangiectasia is a loss-of-function mutation in the ATM gene (ATM 5; ataxia telangiectasia mutated). Besides p53, what
What role do tumor suppressors, including p53, play in mediating cell cycle arrest for cells with DNA damage?
Leland Hartwell, the third recipient of the 2001 Nobel Prize in Physiology or Medicine, was acknowledged for his characterization of cell cycle checkpoint pathways in the budding yeast S. cerevisiae. What is a cell cycle checkpoint pathway? When during the cell cycle do checkpoint pathways
Meiosis and mitosis are overall analogous processes involving many of the same proteim. However, some proteins function uniquely in each of these cell-division events. Explain the meiosis-specific function of the following:a. lme2,b. Rcc8,c. Monopolin.
Describe the series of events by which the APC/C promotes the separation of sister chromatids at anaphase?
Describe how cells know whether sister kinetochores are properly attached to the mitotic spindle?
In 2001, the Nobel Prize in Physiology or Medicine was awarded to three cell-cycle scientists. Paul Nurse was recognized for his studies with the fission yeast S. pombe, in particular for the discovery and characterization of the wee1+ gene. What did the characterization of the wee 1 gene tell
For S phase to be completed in a timely manner, DNA replication initiates from multiple origins in eukaryotes. In S. cereuisiae, what role do S-phase CDKs and DDK complexes play to ensure that the entire genome is replicated once and only once per cell cycle?
A common feature of cell cycle regulation is that the events of one phase ensure progression into a subsequent phase. In S. cerevisiae, G1 and G1/S phase CDKs promote S-phase entry. Name two ways in which they promote the activation of S phase?
The Rb protein has been called the "master brake" of the cell cycle. Describe how the Rb protein acts as a cell cycle brake. How is the brake released in mid- to late G1 to allow the cell to proceed to the S phase?
What is the functional definition of START? Cancer cells typically lose START control. Explain how the following mutations, which arc found in some cancer cells, lead to a bypass of START controls:(a) Over-expression of cyclin D,(b) Loss of Rb function,(c) Loss of p 16 function,(d) Hyperactive E2F?
Explain the role of CDK inhibitors. If cyclin-CDK complexes are required to allow regulated progression through the eukaryonc cell cycle, what would be the physiological rationale for CDK inhibitors?
Explain how CDK activity is modulated by the following proteins:(a) Cyclin,(b) CAK,(c) Weel,(d) p21.
ln Xenofms, one of the substrates of mitotic CDKs is the Cdc25 phosphatase. When phosphorylated by mitotic CDKs, Cdc25 is activated. What is the substrate of Cdc25? How does this information help to explain the rapid rise in mitotic CDK activity as cells enter mitosis?
What physiological differences between S. pombe and S. cerevisiae make them useful yet complementary tools for studying the molecular mechanisms involved in cell cycle regulation and control?
What experimental evidence indicates that cyclin B is required for a cell to enter mitosis? What evidence indicates that cyclin B must be destroyed for a cell to exit mitosis?
Tim Hunt shared the 2001 Nobel Prize in Physiology or Medicine for his work in the discovery and characterization of cyclin proteins in eggs and embryos. Describe the experimental steps that led him to his discovery of cyclins?
What types of experimental strategies do researchers employ to study cell cycle progression? How can these strategies differ based on generic versus biochemical approaches?
What cellular mechanism(s) ensure that passage through the cell cycle is unidirectional and irreversible? What molecular machinery underlies these mechanism(s)?
The PI3K/AKT signaling pathway is aberrant in a wide variety of cancers. In soft-tissue sarcoma (STS) cells, AKT1 activation induces cell motility and invasiveness, which leads to aggressive metastasis of the cells. AKTl was shown to bind to vimentin (see Q-S Zhu eta!., 2010, Vimentin is a novel
Kinesin-1 contains two identical heavy chains and therefore has two identical motor domains. In contrast, kinesin-5 contains four identical heavy chains. Electron microscopic analysis of metal-shadowed kinesins results in the images shown in the top panel. Pretreatment of these kinesins with an
Growth cones are highly mobile regions of developing neurons. What prevents the growth cone from moving or collapsing back into the main cell body like often occurs with lamellipodia?
Explain why there are no known motors that use intermediate filaments as tracks.
The best strategy for treating a specific type of human tumor can depend on identifying the type of cell that became cancerous to give rise to the tumor. For some tumors that have metastasized (moved) to colonize a distant location, identifying the parental cell type can be difficult. Because the
Cytokinesis, the process of cytoplasmic division, occurs shortly after the separated sister chromatids have neared the opposite spindle pules. How is the plane of cytokinesis determined? What are the respective roles of microtubules and actin filaments in cytokinesis?
Anaphase B involves the separation of spindle poles. What forces have been proposed to drive this separation? What underlying molecular mechanisms are thought to provide these forces?
The poleward movement of kinetochores, and hence chromatids, during anaphase A requires that kinetochores maintain a hold on the shortening microtubules. How does a kinetochore hold on to shortening microtubules?
Mitotic spindle function relics heavily on microtubule motors. For each of the following motor proteins, predict the effect on spindle formation, function, or both of adding a drug that specifically inhibits only that motor: kinesin-5, kinesin-13, and kinesin-4.
The mitotic spindle is often described as a micro-tubulebased cellular machine. The microtubules that constitute the mitotic spindle can be classified into three distinct types. What are the three types of spindle microtubules, and what is the function of each?
What effect would dynein inactivation have on kinesin- 2-dependent IFT transport?
Cell swimming depends on appendages containing microtubules. What is the underlying structure of these appendages, and how do these structures generate the force required to produce swimming?
What features of the dynactin complex enable cytoplasmic dynein to transport cargo toward the microtubule (-) end? What effect could inhibition of dynactin interactions with the +TIP EB-1 have on spindle orientation in cells?
The motile properties of kinesin motor proteins involve both the motor domain and the linker domain. Describe the role of each domain in kinesin movement, direction of movement, or both. Could kinesin-1 with one inactive head efficiently move a vesicle along a microtubule?
Certain cellular components appear to move bidirectionally on microtubules. Describe how this is possible given that microtubule orientation is fixed by the MTOC.
Kinesin-1 was the first member of the kinesin motor family to be identified and therefore is perhaps the best-characterized family member. What fundamental property of kinesin was used to purify it?
Many drugs that inhibit mitosis bind specifically to tubulin, microtubules, or both. What diseases are such drugs used to treat? Functionally speaking, these drugs can be divided into two groups based on their effect on microtubule assembly. What are the two mechanisms by which such drugs alter
Microtubulcs within a cell appear to be arranged in specific arrays. What cellular structure is responsible for determining the arrangement of microtubules within a cell? How many of these structures are found in a typical cell? Describe how such structures serve to nucleate microtubule assembly.
In cells, microtubule assembly depends on other proteins as well as tubulin concentration and temperature. What types of proteins influence microtubule assembly in vivo, and how does each type affect assembly?
Microtubules both in vitro and in vivo undergo dynamic instability, and this type of assembly is thought to be intrinsic to the microtubule. What is the current model that accounts for dynamic instability?
Microtuhules are polar filaments; that is, one end is different from the other. What is the basis for this polarity, how is polarity related to microtubule organization within the cell, and how is polarity related to the intracellular movements powered by microtubule-dependent motors?
Microtuhules are polar filaments; that is, one end is different from the other. What is the basis for this polarity, how is polarity related to microtubule organization within the cell, and how is polarity related to the intracellular movements powered by microtubule-dependent motors?
Myosin Vis an abundant nonmuscle myosin that is responsible for the transport of cargo such as organelles in many cell types. Structurally, it consists of two identical polypeptide chains that dimerize to form a homodimer. The motor domains reside at theN-terminus of each chain and contain both
Cell motility has been described as being like the motion of tank treads. At the leading edge, actin filaments form rapidly into bundles and networks that make protrusions and move the cell forward. At the rear, cell attachments are broken and the tail end of the cell is brought forward. What
To move in a specific direction, migrating cells must utilize extracellular cues to establish which portLOn of the cell will act as the front and which will act as the back. Describe how G proteins appear to be involved in the signaling pathways used by migrating cells to determine direction of
Several types of cells utilize the actin cytoskeleton to power locomotion across surfaces. How are different assemblies of actin filaments involved in locomotion?
Phosphorylation of myosin light-chain kinase (MLCK) hy protein kinase A (PKA) inhibits MLCK activation by Ca2+ calmodulin. Drugs such as albuterol bind to β-adrenergic receptor, which cause a rise in cAMP in cells and activation of PKA activity. Explain why albuterol is useful for treating the
Contraction of both skeletal and smooth muscle is triggered by an increase in cytosolic Ca2+. Compare the mechanisms by which each type of muscle converts a rise in Ca2+ into contraction.
Myosin II has a duty ratio of 10 percent, and its step sizeis 8 nm. In contrast, myosin V has a much higher duty ratio (about 70 percent) and takes 36-nm steps as it walks down an actin filament. What differences between myosin II and myosin V account for their different properties? How do the
How does myosin convert the chemical energy released by ATP hydrolysis into mechanical work?
Contractile bundles occur in nonmuscle cells; these structures are less organized than the sarcomeres of muscle cells. What is the purpose of nonmuscle contractile bundles? Which type of myosin is found in contractile bundles?
The ability of myosin to walk along an actin filament may be observed with the aid of an appropriately equipped microscope. Describe how such assays are typically performed. Why is ATP required in these assays? How can such assays be used to determine the direction of myosin movement or the force
There are at least 20 different types of myosin. What properties do all types share, and what makes them different? Why is myosin II the only myosin capable of producing contractile force?
Compare and contrast the ways in which formin and WASp arc activated, and how each stimulates actin filament formation.
Predict how ·actin would polymerize on an arrowhead decorated seed (as shown in the following Figure) in the presence of CapZ, tropomodulin, or profilin-actin. (+) end end
Although purified actin can assemble reversibly in vitro, various actin-binding proteins regulate the assembly of actin filaments in the cell. Predict the effect on a cell's actin cytoskeleton if function-blocking antibodies against each of the following are independently microinjected into cells:
Actin filaments at the leading edge of a crawling cell are believed to undergo treadmilling. What is treadmilling, and what accounts for this assembly behavior?
The predominant forms of actin inside a cell are ATP-Gactin and ADP-F-actin. Explain how the interconversion of the nucleotide state is coupled to the assembly and disassembly of actin subunits. What would be the consequence for actin filament assembly/disassembly if a mutation prevented actin's
Much of our understanding of actin assembly in the cell is derived from experiments using purified actin in vitro. What techniques can be used to study actin assembly in vitro? Explain how each of these techniques works. Which of these techniques would tell you whether the mass of actin filaments
In cells, actin filaments form bundles and/or networks. How do cells form such structures, and what specifically determines whether actin filaments will form a bundle or a network?
Actin filaments have a defined polarity. What is filament polarity? How is it generated at the subunit level? How is filament polarity detectable?
Three systems of cytoskeletal filaments exist in most eukaryotic cells. Compare them in terms of composition, function, and structure.
1. G. Johnson and colleagues have analyzed the MAP kinase cascade in which MEKK2 participates in mammalian cells. By a yeast two-hybrid screen (see Chapter 7), MEKK2 was found to bind MEK5, which can phosphorylate a MAP kinase. To elucidate the signaling pathway transduced by MEKK2 in vivo, the
What biochemical reaction is catalyzed by γ-secretase? Why was it proposed that a chemical inhibitor of this activity might be a useful drug for treating Alzheimer's disease? What possible side effects of such a drug would complicate this use?
What feature of Delta ensures that only neighboring cells are signaled?
Describe two roles for polyubiquitination in the NK-KB signaling pathway.
Why is the signaling pathway that activates NF-KB considered to be relatively irreversible compared with cytokine or RTK signaling pathways? Nonetheless, NF-KB signaling must be down-regulated eventually. How is the NF-KB signaling pathway turned off?
Most mammalian cells have a single immobile cilium called the primary cilium, in which intraflagellar transport (1FT) microtubule motor proteins move elements of the Hedgehog (Hh) signaling pathway. What parts of the Hh signaling pathway would mutations in the IFT motor proteins Kif3A, Kif7, and
Explain why loss-of-function hedgehog and smoothened mutations yield the same phenotype but a loss-of-function patched mutation yields the opposite phenotype in flies.
The extracellular signaling protein Hedgehog can remain anchored to cell membranes. What modifications to Hedgehog enable it to be membrane bound? Why is this property useful?
How is the signal generated by binding of TGF-13 to cellsurface receptors transmitted to the nucleus, where changes in target gene expression occur? What activity in the nucleus ensures that the concentration of active Smads closely reflects the level of activated TGF-13 receptors on the cell
Binding of TGF-13 to its receptors can elicit a variety of responses in different cell types. For example, TGF-13 induces plasminogen activator inhibitor in epithelial cells and specific immunoglobulins in B cells. In both cell types, Smad3 is activated. Given the conservation of the signaling
Describe the function of the PTEN phosphatase in the PI-3 kinase signaling pathway. Why is a loss-of-function mutation in PTEN cancer promoting? Predict the effect of constitutively active PTEN on cell growth and survival.
Describe the events required for full activation of protein kinase B. Name two effects of insulin mediated by protein kinase B in muscle cells.
The enzyme Stell participates in several distinct MAP kinase signaling pathways in the budding yeast S. cerevisiae. What is the substrate for Ste 11 in the mating factor signaling pathway? When a yeast cell is stimulated by mating factor, what prevents induction of osmolytes required for survival
A mutation in the Ras protein renders Ras constitutively active (RasD). What is constitutive activation? How is constitutively active Ras cancer promoting? What type of mutation might render the following proteins constitutively active:(a) Smad3(b) MAP kinase(c) Nf-KB?
Once an activated signaling pathway has elicited the proper changes in target gene expression, the pathway must be inactivated. Otherwise, pathologic consequences may result, as exemplified by persistent growth factor-initiated signaling in many cancers. Many signaling pathways possess intrinsic

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Molecular Cell Biology 7th edition Harvey Lodish, Arnold Berk, Chris A. Kaiser, Monty Krieger, Anthony Bretscher, Hidde Ploegh, Angelika Amon, Matthew P. Scott - Solutions

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