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BL A512 -- Signal Transduction Fall -- 1998 -- Prof. Stark
Midterm Exam -- March 3, 1998 -- 100 points

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1. Name four amino acids which are phosphorylated in signalling systems in eukaryotes and prokaryotes? (4 points)



2. Show with an equation and / or a graph how the unit Siemens is related to Ohm's law. (2 points)




3. Where in the G-protein linked receptor are the (a) glysosylation (b) G-protein interaction and (c) phosphorylation sites? (3 points)




4. Draw the general structures of insulin (and how that structure relates to proinsulin) and the insulin receptor (and how its subunits are positioned in the membrane. (3 points)




5. For voltage to gate activation of the action potential's sodium channel or the Shaker potassium channel, what happens to what part of the molecule? (2 points)



6. What kind of a "filter" (in terms of the frequency pass of the RC circuit) is a glass micropipette and why is this time constant so high in terms of the duration of fast signals like the action potential? (2 points)



7. What molecule donates the phosphate to phosphorylate the sodium potassium pump? (1 point)


8. Why is the potential calculated by the Nernst equation called an equilibrum potential? (1 points)


9. What is the term used to describe the kind of mechanoreceptor in the fingertips which would be used to detect the roughness of a surface while running the fingertips over that surface? (1 point)


10. Where is dystrophin in relation to a mechanogated channel? How did dystrophin get its name? (2 points)


11. What are the two interesting intracellular domains of the CFTR? (2 points)


12. What were the general strategies used in the first isolations of the sodium channel from Electrophorus and the Shaker potassium channel from Drosophila. To find a mouse homologue of the Drosophila Shaker channel, what is done? (3 points)



13. SNARE stands for SNAP receptor. Where (cellular compartments) are SNARE and SNAP? (2 points)



14. Compare the concentration (number per unit of area) of nicotinic acetylcholine receptors at the end plate with the axonal sodium channel. (2 point)


15. What happens to the conductance of the chloride channel during an inhibitory post-synaptic potential (IPSP) triggered by an inhibitory neurotransmitter like GABA? (1 point)


16. What does botulism toxin do in the nervous system and what protein is specifically affected? (2 points)


17. Here is part of a diagram redrawn from Berridge's 1985 Scientific American paper on intracellular communication. Draw a corrected diagram for receptor and G-protein taking into account present knowledge about membrane localization and subunit structure. (3 points)





18. What two molecules are ADP-ribosylated by the actions of what two respective toxins, and what does that do to the action of those two molecules? (4 points)




19. Discuss the NMDA receptor with respect to (a) type (e.g. enzyme, G-protein linked, ionotropic, etc), (b) the way this receptor activates neuronal nitric oxide synthase, and (c) the mechanism of facilitating the receptor - NOS interaction. (3 points)



20. The small GTP binding protein Ras requires a GEF (guanine nucleotide exchange factor, alias GNRP = guanine nucleotide releasing protein) and a GAP (GTPase activating protein). By contrast, how does the alpha subunit of the heterotrimeric G protein perform these functions? (2 points)



21. What is unusual about cAMP signalling as the Dictyostellum aggregation pheromone system as compared with the Gs system? In other words, compare location of action and molecule with which cAMP interacts. (4 points)



22. How is a CFTR homologue related to yeast mating? (1 point)


23. What is the membrane receptor for the subunit of cholera toxin which facilitates the entry into the cell of the other subunit which interacts with the G protein? (1 point)


24. What alteration is made to what amino acids on what portion of the bacterial chemoreceptor protein to mediate adaptation at the receptor level? (3 points)



25. Describe the geometry of the protein used in gap junctions from the standpoint of number of membrane spans per protein, number of proteins per unitary channel, relationship of such channels in two communicating cells, and arrangement (number or geometry) of unitary channels per gap junction. (4 points)




26. What enzyme makes an amino acid derivative into a monamine neurotransmitter such as a catecholamine? (1 point)


27. What molecule mediates the calcium dependence of the potassium channel of Paramecium . By contrast, what is the calcium-binding protein mechanism for vesicle release? (2 points)


28. Describe the neurotransmitter ligand channel. For instance, what is the configuration of the membrane spanning region(s) of each protein subunit? For the nicotinic acetylcholine receptor, what is the arrangement of subunits? (3 points)



29. How does cAMP regulate PKA? How is cAMP's action ended, and what common drug inhibits this process? (3 points)



30. Where is the IP3 receptor located? (1 point)


31. Where is adenylyl cyclase located and what causes it to be located there? (2 points)


32. In bacterial chemotaxis, ligand (aspartate) activates receptor (Tar) which, in turn activates kinase regulator (cheW) to regulate autophosphorlation of cheA. Where does CheA get its phosphate from, and what two molecules does it donate its phosphate to? (3 points)


33. Give two of the original pieces of evidence that the chemoreceptor system in bacteria did not depend on metabolism of nutrients? How many different types of receptors are there now thought to be in E. coli? (3 points)



34. What would a disorder of the human homologue of the ether-a-go-go gene's potassium channel do to the electrocardiogram? (1 point)


35. How (if at all) does the G protein differ in signalling pathways which involve PKA vs PKC? (2 points)



36. What is the relative size of the alpha subunit of the heterotrimeric G protein vs. the ras protein? (1 point)


37. Carbon monoxide is synthesized from heme. By contrast, what is the precursor for nitric oxide? Also, by contrast, what does heme have to do with nitric oxide synthesis? (2 points)



38. What would happen to the end plate potential and why if the concentration of extracellular calcium were decreased? (2 points)


39. Behaviorally, how does a bacterium wind up approaching an attractant? (1 point)


40. What is unusual about the GC involved in the sea urchin spermatozoan attraction to the peptide released by the egg and for atrial natriuretic peptide? (1 point)


41. In the somatic motor system, the nicotinic receptor is at the end plate. By contrast, in the autonomic motor system, where, if at all, is the nicotinic receptor used? (2 points)


42. What is unusual about how the nervous system mediates regulates the vascular smooth muscle in the corpus cavernosum? What is the mediator derived from the endothelium liberated through the effects of that unusual transmitter mechanism? (2 points)



43. Stock et al. propose that cheY is analogous to ras. What would be the specific analogues of activated ras (ras-GTP), inactivated ras (ras-GDP), and GAP? (3 points)



44. What are the respective predominant mechanisms for removing acetylcholine vs. norepinephrine from the synaptic cleft? (2 points)


45. What is special about arachidonic acid in terms of its structure and its products? (2 points)



46. Give an example of a ligand-gated channel gated from the inside of the cell. (1 point)



47. What kind of molecule is a response element part of? (1 point)



48. How much ATP, if any, is utilized to operate the sodium channel which mediates the action potential? (1 point)


49. What is muscarine? (1 point)


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