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Science 19 February 1993:
Vol. 259. no. 5098, pp. 1169 - 1172
DOI: 10.1126/science.8438167
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Articles

Science, Vol 259, Issue 5098, 1169-1172
Copyright © 1993 by American Association for the Advancement of Science

articles

A functional role for GTP-binding proteins in synaptic vesicle cycling

SD Hess, PA Doroshenko, and GJ Augustine

Department of Biological Sciences, University of Southern California.

The squid giant synapse was used to test the hypothesis that guanosine-5'-triphosphate (GTP)-binding proteins regulate the local distribution of synaptic vesicles within nerve terminals. Presynaptic injection of the nonhydrolyzable GTP analog GTP gamma S irreversibly inhibited neurotransmitter release without changing either the size of the calcium signals produced by presynaptic action potentials or the number of synaptic vesicles docked at presynaptic active zones. Neurotransmitter release was also inhibited by injection of the nonhydrolyzable guanosine diphosphate (GDP) analog GDP beta S but not by injection of AIF4-. These results suggest that a small molecular weight GTP-binding protein directs the docking of synaptic vesicles that occurs before calcium-dependent neurotransmitter release. Depletion of undocked synaptic vesicles by GTP gamma S indicates that additional GTP-binding proteins function in the terminal at other steps responsible for synaptic vesicle replenishment.


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