Exam #4 Review Questions

21. What is a GAP? If you increased the amount of a GAP, how would that affect a GPCR signaling pathway? (Would the presence of a GAP lead to an increase or decrease in the effector response?)

GAPs are GTPase Activating Proteins. The intrinsic GTPase activity (hydrolysis of GTP to GDP) is sped up by GAPs. If you increased the amount of a GAP, a GPCR signaling pathway would decrease its effector response.

17. What are GPCRs? How many transmembrane domains do they have? Why are they called GPCRs?

GPCRs are G-protein coupled receptors. These receptors interact with trimeric G-proteins on the intracellular side. They all have seven transmembrane domains.

13. How are kinetochores attached to microtubules? Understand how the structure allows movement of the chromosomes to spindle poles.

Kinetochores are attached to microtubules via a collar structure at the MT plus end. This allows polymerization and depolymerization to occur at the exposed plus end while the MT remains attached to the kinetochore. When depolymerization occurs, the protofilaments of the microtubule curl outward and push against the collar structure. This moves the kinetochore toward the MT minus end at the spindle pole.

12. What type of molecule is ghrelin? What type of signaling does it participate in? What cell type releases ghrelin? Where are the cells that respond to ghrelin located? What is the function of ghrelin?

Ghrelin is a hormone produced mainly by endocrine cells in the stomach. They participate in endocrine signaling. Ghrelin travels through the circulatory system to the hypothalamus in the brain. Ghrelin functions to indicate hunger.

20. What is a GEF? Why are GPCRs considered GEFs? Can trimeric G proteins be activated in the absence of GEFs?

A GEF is a guanine nucleotide exchange factor. These are factors that increase G protein exchange of GDP for GTP. GPCRs are considered GEFs when they activate trimeric G proteins. Trimeric G proteins cannot be activated in the absence of GEFs.

4. Describe negative and positive feedback loops. What do these feedback loops allow pathways to do?

A positive feedback loop occurs when a product of a pathway stimulates its own production or activation. A negative feedback loop occurs when a product of a pathway inhibits an earlier step in the same pathway. These feedback loops allow pathways to terminate and or amplify certain signals.

36. What do you think would happen to this pathway if a GAP targeting Ras was present?

If a GAP targeting Ras was present, the effector response would decrease.

22. If a cell had a loss of function mutation in a trimeric G protein subunit that led to the production of trimeric G proteins that could not bind GPCRs, could GPCRs still signal in a way that led to the desired effector response? Why or why not? Could ligands still bind GPCRs

If a cell had a loss of function mutation in a trimeric G-protein subunit that led to the production of trimeric G proteins that could not bind GPCRs, GPCRs could not still signal in a way that led to the desired effector response. If the G protein could not bind GPCRs, the GPCR could not act as a GEF, and thus the G protein would not be able to be activated to be able to interact with the target molecule. Ligands could still bind GPCRs.

27. What would happen if arrestin was not functional, or GPCR phosphorylation did not occur?

If arrestin was not functional, or GPCR phosphorylation did not occur, receptor desensitization would not occur. GRK phosphorylates the GPCR on multiple sites, and arrestin usually binds to the phosphorylated GPCR.

28. Describe how enzyme-linked receptors function.

Enzyme-linked receptors are transmembrane receptors that function when the binding of an extracellular ligand causes enzymatic activity on the intracellular side. Two inactive catalytic domains are joined and activated by the dimer signal molecule. The receptor protein is either an enzyme itself or it associates directly with an enzyme; ligand binding triggers enzymatic activity.

3. What are the structural and mechanistic differences between prokaryotic and eukaryotic flagella?

Prokaryotic flagella have a structure composed of a membrane-bound motor complex driving propeller-like movement of the extracellular flagellum. Prokaryotic flagellum is composed of the helical protein flagellin (NO MICROTUBULES). Eukaryotic flagella (sperm) are complex microtubular structures that extend out from the cell body under the plasma membrane (extend out from basal bodies). Immobilized dynein pulls to bend the microtubule. Relaxation or a counter pull creates waving. They rely on axoneme bending as their mechanism of motion.

31. What does RTK stand for and why are they called that? What happens when a ligand binds to RTKs?

RTK stands for receptor tyrosine kinase; they are called that because they phosphorylate tyrosine residues. When a ligand binds to RTKs, it causes dimerization and cross-phosphorylation.

30. What domain do all RTK subfamilies share?

RTK subfamilies all have intracellular kinase domains!

29. What type of receptors are RTKs?

RTKs are a class of enzyme-linked cell surface receptors.

33. What type of protein is Ras?

Ras is a monomeric GTPase (g-protein).

15. Leptin is produced in adipose cells, therefore obese individuals tend to have higher levels of leptin in circulation. However, in these individuals high leptin does not correspond to a reduction of food intake. Explain what might be going on.

Receptor desensitization is occurring.

11. What is the cause and consequence of receptor desensitization? Name and describe three mechanisms of receptor desensitization.

Receptor desensitization is the uncoupling of a receptor from its signaling cascade, and occurs after prolonged exposure to the ligand. 1. *Inactivation*: a receptor is altered in a way that disconnects it from its cascade. 2. *Sequestration*: a receptor is temporarily internalized (removed from the membrane). 3. *Down-regulation*: a receptor is destroyed in a lysosome after internalization.

18. What are trimeric G proteins? How are they activated and inactivated? What exactly happens after a ligand binds the GPCR?

Trimeric G proteins are proteins composed of three subunits that are activated via GTP binding. G proteins are inactivated when the G protein hydrolyzes its bound GTP to GDP. After a ligand binds the GPCR, the GPCR acts as a GEF (guanine nucleotide exchange factor) by causing the alpha subunit to release GDP, thereby allowing GTP to bind. This results in a conformational change that allows the active alpha subunit and beta-gamma subunit to interact with targets.

14. A cell begins to migrate toward a chemotactic signal. What would happen if a GAP prematurely targeted Rho-GTPase as the cell was starting to migrate? Would stress fibers form? Explain your answer (be sure to discuss specific pathway targets and effector responses; be sure to understand what a stress fiber is).

When GAPs are present they inhibit the ability of GTPases to activate their target proteins. Therefore, if a GAP prematurely targeted Rho-GTPase as the cell was starting to migrate, contraction would not occur because the rho-dependent kinase would not be activated. This would prevent stress fiber formation, prevent integrin clustering, prevent focal adhesion formation, and decrease myosin activity.

13. A cell begins to migrate toward a chemotactic signal. What would happen if a GAP prematurely targeted the Rac-GTPase as the cell was starting to migrate? Explain your answer (be sure to discuss specific pathway targets and effector responses)

When GAPs are present they inhibit the ability of GTPases to activate their target proteins. Therefore, if a GAP prematurely targeted the Rac-GTPase as the cell was starting to migrate, protrusion would not occur because the rac-dependent kinases would not be activated. This would inhibit treadmilling of branched actin web of the lamellipodia, and not prevent stress fibers from forming in the front.

19. What happens to the G protein when the GTP bound to a G Protein is hydrolyzed to GDP? (How does it affect activity and protein structure?)

When the GTP bound to a G-protein is hydrolyzed to GDP, inactivation occurs, and the subunits stop interacting together, and thus stop interacting with target molecules/proteins.

9. How do ciliary and flagellar axonemes bend? What would happen if the adjacent microtubule pairs were not connected by nexin? Why?

When the motor domain of dynein is activated, it tries to "walk" along the neighboring doublet microtubules. Usually, this would cause one doublet to "slide", but because of nexin, sliding is prevented and the force causes bending. Sliding would occur in the absence of Nexin, which holds adjacent doublets together as dynein exerts motive force.

12. What are the molecular mechanisms of chemotaxis during cell migration? (Hint: your answer should involve Rac and Rho)

*Protrusion* (chemotaxis at the front) 1. Cell surface transmembrane receptors 2. Rac GTPase 3. Rac-dependent kinases 4. Increases: ARP, filamin, profilin, cofilin Decreases: capping protein, myosin activity 5. Localized effector response: treadmilling of branched actin web in lamellipodia; less stress fibers in front. *Contraction* (chemotaxis at the back) 1. Cell surface transmembrane receptors 2. Rho GTPase 3. Rho-dependent kinase 4. Increases: myosin activity, formin, actinin Decreases: cofilin, ARP, filamin 5. Localized effector response: stress fiber formation, integrin clustering, focal adhesion formation, myosin activity.

7. Describe the ligands involved in each type of signaling. -Juxtacrine ligands: -Paracrine ligands: -Endocrine ligands: -Synaptic ligands:

-Juxtacrine ligands: Membrane bound ligands, ECM molecules, or small cytoplasmic molecules. -Paracrine ligands: Growth factors (proteins that stimulation growth), cytokines (generic term for most other small signaling proteins), gases (NO, CO). -Endocrine ligands: hormones (released into the bloodstream) -Synaptic ligands: neurotransmitters (released by neurons, received by neurons, muscles, or glands.

6. Briefly describe the following types of signaling: -Juxtacrine signaling: -Paracrine signaling: -Endocrine signaling: -Synaptic signaling:

-Juxtacrine signaling: Signal to neighboring cell only. (contact dependent) -Paracrine signaling: local diffusion; further than neighboring cells but generally target cells within a tissue (NOT systemic) -Endocrine signaling: systemic, long distance diffusion in circulatory system. -Synaptic signaling: short distance diffusion, systemic action; signal specifically between cells within a structure called the synapse.

10. Describe the steps involved in cell migration ("crawling").

1. Chemotaxis (attracts or repels cells) 2. Protrusion (actin filament treadmilling pushes the front of the cell) 3. Attachment and traction (actin-cytoskeleton connects across the plasma membrane to the substratum, allows cell to generate traction; the bulk of the trailing cell is translocated forward with the help of actin-myosin) 4. Contraction/retraction (contractile actin bundles called stress fibers facilitate contraction at the rear).

26. Describe all of the steps of the PLC pathway. (Be sure to understand the mechanisms of all steps and note the enzyme that is activated by the trimeric G protein and what the amplification step is in this pathway.)

1. Ligand binds GPCR, causing the activation of G protein. 2. Activated G protein triggers activation of phospholipase C (PLC), an enzyme that catalyzes the breakdown of PIP2 into DAG and IP3 (2nd messengers!). THIS IS THE AMPLIFICATION STEP! 3. DAG stays imbedded in the plasma membrane. IP3 binds to calcium channels in the ER membrane. This causes the release of calcium (2nd messenger!) into the cytosol. 4. Calcium binds to protein kinase C (PKC), which triggers PKC to translocate from the cytosol to the membrane. 5. DAG activates PKC in the membrane. 6. PKC can phosphorylate various target molecules!

23. Describe all of the steps of the cyclic AMP pathway. (Be sure to understand the mechanism of all steps; note the enzyme that is activated by the trimeric G protein and what the amplification step of the pathway is.)

1. Ligand binds GPCR, causing the activation of G protein. 2. G protein activates adenylyl cyclase. 3. Adenylyl cyclase converts ATP to cAMP (2nd messenger!) THIS IS THE AMPLIFICATION STEP! 4. cAMP activates PKA via a negative allosteric interaction with inhibitory subunits. 5. Activated PKA translocates to the nucleus and phosphorylates CREB. 6. Phosphorylated CREB recruits its transcriptional co-activator CBP. 7. Target genes are transcribed.

5. What are the different types of flagellar swimming and how are they different?

1. Linear "running": flagella all work together to propel the bacteria forward in a straight line. 2. Tumbling: one or more flagella move in an opposite direction; causes bacteria to temporarily stall.

18. Describe the complete molecular mechanism of contraction. (Include the actions of Ach, Ca2+, tropomyosin, troponin, myosin and actin in your answer.)

1. Neuron releases Ach. 2. Ach binds to ligand-gated ion channels to cause an AP in the muscle cell. 3. The action potential leads to the release of calcium in the cell. 4. Calcium binds to troponin and causes it to move tropomyosin, which allows myosin to bind actin 5. Once myosin can bind actin, it can mediate contraction.

38. What are the two types of intracellular receptors?

1. Nuclear receptors 2. Soluble gas receptors

1. What are the different strategies cells use to move and what are the mechanisms of each strategy?

1. Swimming 2. Crawling 3. Contraction

35. Describe the steps of the Ras-MAPK pathway (again, know the steps and understand the mechanisms).

1. When a ligand binds RTKs it causes two RTK monomers to form a dimer, which causes their intracellular kinase domains to cross-phosphorylate each other on tyrosine (Tyr) residues. 2. The phosphorylated Tyr residues serve as binding sites for an adaptor protein called Grb2. 3. Sos (a Ras-GEF) binds to Grb2. 4. Sos binding to Ras on the membrane triggers Ras to release GDP, which allows GTP to bind in its place. 5. Ras (in the GTP bound state) activates the MAP kinase cascade, which consists of three serine/threonine kinases. 6. Raf (the MAP kinase kinase kinase) is activated, which then phosphorylates Mek (the MAP kinase kinase), which then phosphorylates Erk (the MAP kinase). 7. Erk then phosphorylates any number of target proteins, depending on the cell type.

9. What happens at the G2/M checkpoint? What could happen if a cell bypassed this checkpoint? What happens to cause a cell to move past this checkpoint?

At the G2/M checkpoint, events are triggered that lead to chromosome alignment during metaphase. This checkpoint will not be passed if DNA replication is not complete or if DNA damage is detected. Instead, the cell cycle will arrest to give the cell time to complete DNA replication or to repair damage. To move past this checkpoint, an abrupt increase in M-cdk activity is required.

11. What happens at the M phase (metaphase-to-anaphase transition) checkpoint? What is APC/C? What proteins do APC/C target and why are these targets important for moving past this checkpoint?

At the M phase checkpoint, if kinetochores are all attached to spindle microtubules during metaphase, anaphase-promoting complex (APC/C) is activated. APC/C is a ubiquitin ligase that targets proteins for destruction by the proteasome: 1. M Cyclin targets lamins for disassembly, activates condensin complex, inhibits myosin; when destroyed by APC/C, allows for assembly of nuclear membrane, DNA de-condenses, and, myosin can aid in contractile ring function. 2. Securin helps to secure sister chromatids together at the metaphase plate; when destroyed by the APC/C, the separation of sister chromatids can occur. When APC/C is active, it promotes progression through cytokinesis; when it is inactive, the cell remains in metaphase.

8. What is autocrine signaling? How is it different from paracrine signaling?

Autocrine signaling occurs when a secreted molecule acts on the same cell that produces it. This is different from paracrine signaling because paracrine signaling involves the diffusion of a ligand further than neighboring (or the same) cells.

5. Describe what crosstalk is and define the two different types of crosstalk.

Crosstalk is when one or more components of a signal transduction pathway affects another pathway. 1. Convergent cross-talk: signals from *different ligands* signaling through unrelated receptors converge on a common intracellular signaling protein or effector after binding their specific ligand. The pathways converge to elicit the *same response*. 2. Divergent cross-talk: signals from the *same ligand* diverge to activate various different intracellular proteins or effectors to elicit *different responses*.

3. What are Cdks? What are cyclins? How is their activity regulated? How are they important to the cell cycle?

Cdks are cyclin-dependent kinases. Cyclins are proteins that are expressed and degraded; when present, the cell moves forward in the cell cycle. There are four classes of cyclins, each defined by the stage of the cell cycle at which they bind Cdks and function. All eukaryotic cells require three of these classes: 1. G1 and G1/S cyclins regulate the G1 checkpoint 2. S cyclins regulate the S phase 3. M cyclins regulate the G2/M checkpoint

11. What directs cell migration?

Cell migration is also guided by chemotaxis; an extracellular attractant or repellent binds chemokine receptors and triggers a signal transduction pathway.

3. Why are signaling pathways so complex? What advantage does the complexity provide?

Cells use the complexity of signal transduction for regulation, and coordination/integration of multiple signals! The more complex the signal transduction cascade, the more control there is!

15. What is the importance of cellular attachment during migration and what molecules are involved?

Cellular attachment during migration involves the binding of Integrin proteins to the ECM + Actin filaments (and this clustering of Integrins with the ECM then forms Focal Adhesions which are key to the attachment and traction process); and this attachment basically then allows for traction of the cell body.

2. List and describe the difference cell cycle checkpoints.

Checkpoints are internal controls to make sure a compromised cell does not divide and that the previous phase is complete before moving on. 1. G1 checkpoint: ensures DNA is not damaged and the environment is favorable. 2. G2/M checkpoint: ensures DNA replication is complete and accurate. 3. M Phase checkpoint (Metaphase-to-Anaphase transition checkpoint): ensures chromatids are attached to spindles.

4. What cell types/organisms are cilia and flagella found in?

Cilia are only found on eukaryotic cells. Flagella are found on various prokaryotes, sperm, and many protozoa.

32. How does RTK cross-phosphorylation activate the receptor?

Cross-phosphorylation activates receptors in two ways: 1. Phosphorylation of tyrosines inside the RTK kinase domain increases the kinase activity. 2. Phosphorylation of tyrosines outside the kinase domain creates high-affinity docking sites for intracellular signaling proteins.

14. What is cytokinesis? Why are actin and myosin important?

Cytokinesis results from the assembly of an actin-myosin ring that gets smaller and smaller as myosin pulls along actin. Microtubules of the mitotic spindle determine the place of the contractile ring.

15. How does p21 cause cell cycle arrest?

DNA damage activates p53. Low p53 causes p21 to be expressed. p21 is a protein that can bind to and inhibit Cdk complexes to cause cell cycle arrest (gives cell a chance to repair damage!).

7. What types of genes are regulated by E2F? (Think about what stage of the cell cycle E2F helps a cell to advance to and what happens during that stage; your answer should be in the form of: "E2F regulates genes important for _________________," and list specific processes in the blank.)

E2F regulates genes important for DNA synthesis and proofreading.

9. How are endocrine and synaptic signaling similar? How are they different?

Endocrine and synaptic signaling are similar in that they both result in systemic (body-wide) action. They are different in that synaptic signaling ligands have short-rage diffusion, whereas endocrine signaling ligands have long distance diffusion. Synaptic signaling is faster and more precise.

10. . What type of molecules are endorphins? What type of signaling do they participate in? What cell type releases them? What happens when endorphins are released by these cells? How are they involved in the placebo effect? What happens if endorphins are misregulated?

Endorphins are neurotransmitters. They participate in synaptic signaling. They are produced by various cells within the CNS in response to different triggers. When endorphins are released by these CNS cells, they can inhibit the transmission of pain, and can affect feelings of pleasure. They are involved in the placebo effect because the expectation of something beneficial happening tricks the hypothalamus into releasing endorphins. When endorphins are misregulated, OCD, depression, and anxiety can result.

2. What are the similarities and differences between flagella and cilia?

Flagella and Cilia are both hair-like appendages that can function as motility machines. In eukaryotes, both are composed of microtubules, dynein, and some associated proteins. Flagella are found on various prokaryotes, sperm, and many protozoa. They perform undulating motions; There are usually only one, or a few flagella per cell. Cilia are only found on eukaryotic cells and are shorter than flagella. They perform whip-like motions. Ciliary beating can propel a single cell or move fluid over the surface of many ciliated cells; usually many cilia per cell!

1. List and describe all of the different phases of the cell cycle.

Interphase: G1, S, and G2 phases M phase: mitosis and cytokinesis G1: production of DNA synthase complexes, repair enzymes, histones, etc. S: DNA synthesis and proofreading (error editing). G2: Kinetochores are refined and finalized. Production of organelles, cytoskeletal proteins, molecular motors, metabolic enzymes, etc.

37. How do ion-channel-coupled receptors work? What is the most common ligand of these receptors? What cell types heavily rely on these receptors and why?

Ion-channel-coupled receptors are involved in rapid synaptic signaling between nerve cells and other electrically excitable target cells such as muscle cells. The most common ligand of these receptors are neurotransmitters. Muscle and nerve cells are most heavily reliant on these receptors because they are most easily electrically excitable.

13. What type of molecule is leptin? What type of signaling does it participate in? What cell type releases leptin? Where are the cells that respond to leptin located? What is the function of leptin? How is leptin similar and different from ghrelin?

Leptin is a hormone that is produced by adipose cells. They participate in endocrine signaling. Leptin travels through the circulatory system to the hypothalamus in the brain. Leptin functions to indicate satiety (fullness). Both ghrelin and leptin work in apposition to one another in the regulation of body weight homeostasis. They act on a common population of neurons.

10. What critical function does the M-Cdk complex have? (List its substrates along with each of their cell cycle functions.)

M-cdk phosphorylates a variety of proteins that cause assembly of the mitotic spindle, kinetochores, and attachment to sister chromatids pairs. M-Cdk phosphorylates.. 1. Condensin: chromosome condensation 2. Lamins: nuclear envelope fragmentation 3. Myosin: phosphorylation of myosin by M-cdk inhibits its ability to contract, which is required for purse-string cytokinesis (contractile ring activity...SHOULD NOT HAPPEN UNTIL THE END OF M PHASE!)

12. Why must M-cyclin be degraded at the metaphase-anaphase transition?

M-cyclin must be degraded at the metaphase-anaphase transition because it M-cyclin would inhibit myosin from contracting and aiding in contractile ring formation. Degrading M-cyclin is also important for the assembly of the nuclear membrane and for DNA de-condensation.

34. What kind of protein is MAPK?

MAPK is a kinase.

14. What is the observed phenotype of mice with mutations in the gene that encodes leptin? What is the molecular basis of this phenotype?

Mice with mutations in the gene that encodes leptin are larger. This is because there is no leptin being created, and thus the fat cells do not have a ligand to bind to trigger the hypothalamus to feel "full". Instead, ghrelin keeps initiating "hunger", but no satiety is ever reached, so the mouse continues to eat and get larger.

17. How can the type of ECM components and integrins expressed on a cell affect the direction of cell migration?

Migrating cells tend to follow ECM tracts toward their target. The integrins (transmembrane proteins) on the cell surface determine these tracts. Different integrins have different affinities for different ECM molecules.

1. What kind of cellular activity can be controlled by cell to cell communication?

Migration, growth, proliferation, survival, apoptosis, differentiation, adhesion...almost any cellular activity can be controlled by cell to cell communication!

5. What are mitogens?

Mitogens are extracellular ligands that can trigger mitosis. They act during G1 phase to initiate signaling pathways that trigger passage of the start checkpoint. Mitogens bind to cell-surface receptors to initiate intracellular signaling pathways.

6. Describe the molecular pathway triggered by mitogens. (Hint: this is a LONG answer; you need to describe the pathway from mitogen all the way to S-cyclin; understand the mechanisms of each protein in the pathway)

Mitogens bind to cell-surface receptors to initiate intracellular signaling pathways. One of the major pathways involves activation of the small GTPase Ras. Once Ras is in its active GTP-bound state it activates a MAP kinase cascade. This MAPK cascade causes the expression of numerous immediate early genes, including the gene regulatory protein Myc. Myc then acts as a transcription factor to increase the expression of delayed-response genes, including G1-cyclin! G1-cyclin then binds its Cdk to form G1-Cdk. To move the cell past the Start/Restriction Checkpoint, G1-Cdk phosphorylates the Retinoblastoma (Rb) family of proteins. Phosphorylation inactivates the Rb proteins by causing them to release gene regulatory protein E2F. E2F acts as a transcription factor by binding to specific DNA enhancer sequences of a wide variety of "G1/S genes" that encode proteins required for S-phase entry, including G1/S-cyclins, S-cyclins, and proteins involved in DNA synthesis and chromosome duplication.

6. Describe the molecular mechanism that determines the type of swimming. (Describe the signaling pathway.)

Most bacteria use chemotaxis to determine directionality. They move toward highest concentration of an attractant (or away from a repellent). Two levels of regulation: 1. Chemotaxis receptor activation (attractant or repellant?) 2. Signal transduction to motor Repellent: 1. activates histidine kinase associated receptor, which activates the histidine kinase CheA. 2. phosphorylated CheA binds flagellar motor, which results in a clockwise rotation or "tumbling" Attractant: 1. inactivates histidine kinase associated receptor 2. CheY is not phosphorylated, and it does not bind the flagellar motor. 3. Counterclockwise rotation, or "linear running".

16. How is the cell body moved forward during migration? (Be sure to describe the molecules involved.)

Myosins transport many cellular components directly, which is critical for moving the rest of the cell forward. Myosin pulls against actin bound to extracellular components.

39. How do nuclear receptors work? What domain is common to all of these proteins? Why?

Nuclear receptors function as transcriptional activators. They bind the ligand in the cytosol, translocate to the nucleus, and bind DNA to influence gene regulation. All nuclear receptors have the DNA-binding domain in common.

16. What type of molecule is oxytocin? What type of signaling does it participate in? What cell type releases oxytocin? Where are the cells that respond to oxytocin located? What is the function of oxytocin?

Oxytocin is a hormone (as well as a neurotransmitter!). It participates in endocrine signaling. It is released by cells in the hypothalamus. Oxytocin signals to cells in various regions of the CNS (and body!). Oxytocin facilitates pair bonding, birth, maternal bonding, lactation, decreases stress and anxiety in a socially-dependent manner.

25. What reaction does PLC catalyze?

PLC catalyzes PIP2 into DAG and IP3.

2. Describe how cellular activities are controlled by signaling pathways? (Is it usually one pathway acting alone on a cell....or not?)

Signal transduction pathways are initiated by a signaling ligand that is produced by a signal producing cell. When the ligand binds to a receptor on the responding cell, a cascade of biochemical reactions occurs within the cell that eventually elicits a particular cellular response. Cell are dependent on multiple extracellular signaling molecules that act in combination to elicit a response.

4. What signals are important at the G1 checkpoint? What happens if cells do not pass the G1 checkpoint?

The G1 checkpoint is critical for entry into the cell cycle. If a cell gets a go-ahead signal at the G1 checkpoint, it enters the cell cycle. If the cell does not receive the go-ahead signal, it will exit the cell cycle, switching into a non-dividing state called the G0 phase (quiessence). G1 checkpoint is regulated by various signals. Growth factors (mitogens) trigger signaling pathways that initiate the cell cycle. Most cells also exhibit anchorage dependence (must be attached to divide). Most cells also exhibit density-dependent inhibition (crowded cells stop dividing). Many single-celled organisms monitor external nutrient availability (will not divide if it is inadequate).

40. What is the nitric oxide (NO) receptor called and what are its two functions? Why is NO important in blood vessels? What would happen in the absence of NO or if guanylyl cyclase had an inactivating mutation?

The NO receptor is called Guanylyl Cyclase, and it acts both as an intracellular receptor for NO, and as an intracellular signaling protein. NO is important in blood vessels because when it is released from endothelial cells and binds to guanylyl cyclase in the cytosol, the smooth muscle surrounding the vessels relaxes, causing the blood vessels to dilate (more blood flow!). In the absence of NO or if guanylyl cyclase had an inactivating mutation, The smooth muscle surrounding the blood vessels would be unable to relax, and thus unable to dilate the vessel walls, which would inhibit the control of blood flow.

8. What is the axoneme? Describe the proteins and how they are connected to form this structure.

The axoneme are the microtubules and associated proteins that form the core of eukaryotic flagellum or cilium. Dynein forms bridges between neighboring doublet microtubules.

7. What is the basal body? Compare and contrast with the MTOC.

The basal body nucleates eukaryotic cilia and flagella at the cell surface. The basal body is composed of a ring of nine triplets (same organization as centrioles within the MTOC). However, the MTOC nucleates microtubules near the nucleus. The 9+2 structure is held together with radial spokes and nexin proteins. Dynein tails are attached to one MT doublet, while globular heads attempt to "walk" on the adjacent doublet. This force causes bending.

24. Is the cyclic AMP pathway only activated in response to a single specific ligand and GPCR to cause one specific response? Explain.

The cAMP pathway is activated by a bunch of different ligands, a ton of different GPCRs, and can cause totally different responses in different cell types!