BL A512 -- Signal Transduction, Fall, 2002, Prof. Stark
Midterm exam -- Tuesday March 5, 2002, 100 points

1. In 1971, it was proposed that the separation of disks from the plasmalemma in the rod outer segment necessitated the intervention of an intracellular signal. At first, calcium ion was proposed, but later, another molecule was identified. What is this other molecule? Discuss the enzymes that make vs break down this mediator of visual transduction in the vertebrate rod. Also, discuss how these enzymes are regulated. (5 points)

2. Discuss the Shaker channel with respect to (a) how its speed and Hodgkin-Huxley parameters differ from those of the late K+ channel of the squid axon action potential, (b) how the molecular size and channel structure differ from the Na+ channel of the squid axon action potential, (c) where its activation is in the molecular structure, and (d) where its inactivation is located in the molecular structure. (4 points)

3. (a) What does rhodopsin kinase do to (b) what residues at (c) what location in the rhodopsin molecule? That allows (d) what molecule to bind to rhodopsin to inactivate it? After all of these actions are reversed, there is still one thing that has to be done to regenerate the native rhodopsin so that it can be excited by light. (e) What is this? (5 points)

4. Provide information centered around cyclooxygenase. (a) Give an example of an inhibitor. (b) What is cyclooxygenase's precursor? (c) What5 are the precursor's properties (d) What enzyme makes this precursor? (e) What is cyclooxygenase's product? (5 points)

5. In addition to serving as black paint in the eyeball, what two supportive functions do retinal pigment epithelial cells provide to the rod outer segments? What happens to these cells after decades of providing this support? (3 points)

6. Adaptation is important in sensory systems. (a) Discuss the usefulness of fast adaptation in the phasic Pacinian corpuscle. (b) What ion regulates adaptation mechanisms in the vertebrate rod and (c) How does it get near the molecules it regulates (e.g. recoverin)? (d) What mediates adaptation in the bacterial aspartate receptor and (e) Why would this be important in this kind of chemotaxis? (5 points)

7. In 2000, Arvid Carlsson shared the Nobel Prize in Physiology and Medicine for his "discoveries concerning signal transduction in the nervous system." Specifically, he was involved in the discovery that dopamine was not just norepinephrine's precursor but also a transmitter. Tell the story of the famous disorder of dopamine deficiency. (a) The disease. (b) Where is dopamine in short supply? (c) What is given to help patients? (d) The precursor of what is given (which is also where the biosynthetic pathway begins) (e) A famous person who has the disease. (5 points)

8. What is it that cAMP activates in its traditional signal transduction cascade? Describe the molecular arrangement for this activation. (3 points)

9. Describe the special situation thought ro apply to maintaining sufficient intracellular calcium ion concentrations if the small amount in the intracellular reticulum becomes depleted. (2 points)

10. Discuss your heart beat from the standpoint of (a) the molecular geometry of the channel that carries the electrical signal from cell to cell, (b) the properties of the ventricular muscle action potential, (c) how that is seen in the electrocardiogram (EKG), and (d) what is at fault in well-known a genetic disorder where the repolarization of those cells is delayed. (4 points)

11. Use what you know about intracellular vs extracellular ion concentrations and channel properties to explain why activating the GABA (gamma amino butyric acid) channel would lead to an IPSP (inhibitory postsynaptic potential). (2 points)

12. Bacterial toxins have been useful in understanding. Tell signal transduction stories about toxins of (a) Vibrio cholerae (cholera toxin), (b) Clostridium botulinum (botulism), (c) Bordetella pertussis (whooping cough), and (d) Clostridium tetani (tetanus toxin). (4 points)

13. For the resting potential and the action potential, the membrane is sometimes represented as two batteries for the two most relevant univalent cations respectively. Discuss how the relative contributions of these two batteries is regulated by variable conductances to these two respective ions during the passage of the action potential. (4 points)

14. The striated neuromuscular junction and the neuroeffector junction of the sympathetic nervous system are models for the two respective mechanisms of neurotransmitter action. Describe the transmitter and its receptor in each of these examples. (4 points)

15. A paper is presented later in this course entitled "Mutation of the Stargardt's disease gene (ABCR) in age-related macular degeneration" where ABCR stands for "ATP-binding casette transporter-retina." Discuss how such a molecule might be related with a famous chloride channel you learned about. (2 points)

16. Experiments addressed toward identifying the way calcium ions regulated a potassium channel in Paramecium identified one of the most famous calcium binding proteins coded by a gene originally named after pantophobiac (pnt) mutants. Name and describe this calcium binding protein. (2 points)

17. What kind of a molecule is insulin and what happened to it after translation to make it take on that particular configuration? Like the receptor for EGF (epidermal growth factor), what type of enzymatic activity does insulin's receptor show? In 1987 Daniel Koshland likened this receptor to the aspartate receptor for bacterial chemotaxis. Why? (In what respect?) (4 points)

18. In addition to IP3 (inositol trisphosphate), PLC makes another "second messenger." What is this other signalling molecule and what does it activate? (2 points)

19. Discuss the heterotrimeric G protein from the standpoint of (a) where it is in the cell, (b) what puts (and keeps) it there, (c) what its G protein-linked receptor interacts with, and (d) what function (also missing in small GTP binding proteins like ras) that receptor fulfills. (4 points)

20. Carotenoids get chopped in half to make vitamin A which becomes the chromophore of the visual pigment rhodopsin. Without getting chopped in half, where do carotenoids (specifically lutein and zeaxanthin) reside in the eye? What useful function might they serve there leading drug companies to add lutein to multi-vitamin pills? (2 points)

21. OK, I'll start by reminding you of some alphabet soup: NSF = N-maleimide sensitive factor and SNAP = soluable NSF sensitive factor. There are two SNAP receptors (SNAREs). Where are they and what do they do? (3 points)

22. OK, I'll start with a similar offering in this question. CREB = cAMP response element binding protein. What is a response element? And what molecule is it on (i.e. where does CREB bind?) (2 points)

23. Discuss the functional geometry for manufacture of NO through excitation of an NMDA receptor. Specifically address (a) What is the natural ligand for the NMDA receptor? (b) What is the signal pathway from receptor to enzyme, (c) What keeps the necessary molecules near eachother? and (d) What molecule does NO regulate? (4 points)

24. Why is coffee a mild stimulant? (2 points)

26. Compare the calcium channels for (a) synaptic vesicle release and (b) the phosphoinositide signalling in terms of what activates the channel. Also, discuss the cellular localization and properties of two types of calcium channels involved in excitation-contraction coupling in striated muscle. (4 points)

27. What are the diverse functions and relative numbers of G protein-coupled receptors in the human body. Speculate on how this overall situation arose over an evolutionary time scale using, as an example, the evolution of color vision genes on the X chromosome in Old World Monkeys, great apes and humans. (4 points)

28. In 1970, Sir Bernard Katz won the Nobel Prize in Physiology and Medicine for work in which he defined the quantum for synaptic transmission. What was this quantum of transmitter? How did lowering the concentration of extracellular calcium ions assist him in making this determination? (2 points)

29. What is the pheromone and the receptor for this pheromone for cell aggregation in the cellular slime mold Dictyostelium discoideum? (2 points)

30. When the glycoside ouabain effects a rapid block of the the Na+-K+ ATPase (sodium-potassium pump), the resting potential only changes a few mV (milli Volts). This is why the pump is called "electrogenic." Why is there a change of a few mV and how come the resting potential does not collapse completely and immediately? (2 points)

31. Structural work on the alpha subunit of the heterotrimeric G protein demonstrated switch I and switch II regions. Recently, it was shown that something made the positions of these switch regions to become more invariant. What was this something? (1 point)

32. What does the G-protein need to do to the phosphodiesterase in the rod to activate it? (In other words, how are the components of PDE altered?) (2 points)

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