Assembly of SNARE Core Complexes Prior to Neurotransmitter Release Sets the Readily Releasable Pool of Synaptic Vesicles
Precise regulation of neurotransmitter release is essential for the normal function of neural networks, but the mechanisms involved are largely unclear. Using superfused synaptosomes, we have studied the readily releasable pool of synaptic vesicles, measured as the amount of release triggered by hyp...
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Published in | The Journal of biological chemistry Vol. 275; no. 36; pp. 27703 - 27707 |
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Main Authors | , |
Format | Journal Article |
Language | English |
Published |
American Society for Biochemistry and Molecular Biology
08.09.2000
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Subjects | |
Online Access | Get full text |
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Summary: | Precise regulation of neurotransmitter release is essential for the normal function of neural networks, but the mechanisms
involved are largely unclear. Using superfused synaptosomes, we have studied the readily releasable pool of synaptic vesicles,
measured as the amount of release triggered by hypertonic sucrose. We show that activation of presynaptic metabotropic glutamate
receptors by dihydroxyphenylglycine and stimulation of protein kinase C by phorbol esters enhance the readily releasable pool
of glutamate. Although the molecular nature of the readily releasable pool is unknown, one possibility is that during its
generation, SNARE proteins form full core complexes, and that core complex formation occurs prior to neurotransmitter release.
To test this possibility, we employed N -ethylmaleimide (NEM), an inhibitor of the ATPase N -ethylmaleimide-sensitive factor that dissociates core complexes, to study the relation of the readily releasable pool to
core complex assembly in synaptosomes. NEM induced a dose-dependent increase in the readily releasable pool of neurotransmitters
but by itself did not trigger release. Direct measurements of core complexes confirmed that NEM caused an increase in the
levels of SNARE core complexes under these conditions. Our data suggest that in the readily releasable pool of synaptic vesicles,
SNARE proteins are fully assembled into core complexes, and that SNARE complex assembly is a target of presynaptic regulation. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 |
ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.C000237200 |