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Still nitric oxide (?)

Udo Merkel merkel at bs4.informatik.uni-stuttgart.de
Fri Jun 19 11:09:57 EST 1992

Newsgroups: bionet.neuroscience
Subject: Still nitric oxide (?)
Distribution: world
Organization: Informatik, Uni Stuttgart, Germany
Keywords: long-term potentiation, synaptic plasticity 

In a previous post I mentioned the possible role of the diffusible
molecule _nitric oxide_ as a retrograde messenger in signalling
long-term potentiation (LTP) from the postsynaptic hippocampal cell
(site of LTP induction) back to the neurotransmitter-release site
opposing it (site of LTP expression).

Schumann & Madison (Science 25(1991)1503) mention that a cytosolic 
adenosine diphosphate ribosyltransferase, which may ribosylate 
G proteins, is activated by sodium nitroprusside, an agent that 
generates nitric oxide. This seems particularly relevant because 
a presynaptic G protein may be necessary for the production of LTP.

Leveque et al (Proc Natl Acad Sci USA 89(1992) 3625) suggest that
a tight physical interaction between the synaptic-vesicle (trans-)
membrane protein _synaptotagmin_ and the voltage-gated calcium channel
could play a role in docking synaptic vesicles at the plasma membrane prior
to rapid neurotransmitter release. These author argue that, at least in
the frog neuromuscular junction, calcium channels controlling transmitter
release are exclusively localized at the active zones where exocytosis
occurs. "The association of synaptotagmin with calcium channels would
site synaptic vesicles in a zone that would be rapidly accessible to
calcium transients. This interaction must be tightly controlled and,
although synaptotagmin possesses an extensive panoply of potential
sites for regulation", they speculate that "voltage-dependent
conformational transitions of the channel protein modulate this
interaction" (page 3628).
They also hold that synaptotagmin has a putative transmembrane segment,
with the N terminus oriented toward the interior of the synaptic vesicles,
but presumably exposed at the surface of the nerve terminal after
exocytosis and thus potentially receptive to circulating agents.

Does the finding of Leveque et al open up a vista as to new candidates
of retrograde messengers in synaptic-plasticity regulation in the brain,
or has nitric oxide still an exclusive place there?

Udo Merkel

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