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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