Questions and Answers of Molecular Cell Biology

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
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
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
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
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
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
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
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).
Individuals with the hereditary disorder ataxia telangiectasia suffer from neurodegeneration, immunodeficiency, and increased incidence of cancer. The genetic basis for ataxia telangiectasia is a
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.
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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.
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
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
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.
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
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
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
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
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
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
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
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
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.
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
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
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
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
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
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
Even though GRB2 lacks intrinsic enzymatic activity, it is an essential component of the epidermal growth factor (EGF) signaling pathway that activates MAP kinase. What is the function of GRB2? What
Explain how expression of a dominant-negative mutant of JAK blocks the erythropoietin (Epo) cytokine signaling pathway.
Erythropoietin (Epo) is a hormone that is produced naturally in the body in response to low O2 levels in the blood. The intracellular events that occur in response to Epo binding to its cell surface
Name three features common to the activation of cytokine receptors and receptor tyrosine kinases. Name one difference with respect to the enzymatic activity of these receptors.

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