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PMID: 8816825 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

SNAP-25 and synaptotagmin involvement in the final Ca(2+)-dependent triggering of neurotransmitter exocytosis.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 93 ·No. 19 ·1996-09-17 ·Pages 10471-6

Mehta PP, Battenberg E, Wilson MC

Abstract

In neurons, depolarization induces Ca2+ influx leading to fusion of synaptic vesicles docked at the active zone for neurotransmitter release. While a number of proteins have now been identified and postulated to participate in the assembly and subsequent disengagement of a vesicle docking complex for fusion, the mechanism that ultimately triggers neuroexocytosis remains elusive. Using a cell-free, lysed synaptosomal membrane preparation, we show that Ca2+ alone is sufficient to trigger secretion of glutamate and furthermore that Ca(2+)-signaled exocytosis is effectively blocked by antibodies and peptides to SNAP-25, a key constituent of the vesicle docking complex. In addition, Ca2+ inhibits the ability of synaptotagmin, a synaptic vesicle protein proposed as a calcium sensor and triggering device, to associate with this docking complex. These results support a model in which Ca(2+)-dependent triggering of neurotransmission at central synapses acts after ATP-dependent potentiation of the docking-fusion complex for membrane fusion.

MeSH Terms
Adenosine Triphosphate/analogs & derivatives,pharmacology Amino Acid Sequence Animals Antibodies/pharmacology Antibody Specificity Blotting, Western Calcium/pharmacology Calcium-Binding Proteins Cations, Divalent/pharmacology Cerebral Cortex/physiology Exocytosis/drug effects,physiology Glutamic Acid/metabolism Intracellular Membranes/drug effects,physiology Kinetics Membrane Glycoproteins/antagonists & inhibitors,immunology,physiology Membrane Proteins Mice Molecular Sequence Data Nerve Tissue Proteins/antagonists & inhibitors,immunology,physiology Peptides/pharmacology Synaptosomal-Associated Protein 25 Synaptosomes/drug effects,physiology Synaptotagmins Trypsin/pharmacology
Chemicals
Antibodies Calcium-Binding Proteins Cations, Divalent Membrane Glycoproteins Membrane Proteins Nerve Tissue Proteins Peptides Snap25 protein, mouse Synaptosomal-Associated Protein 25 Synaptotagmins adenosine 5'-O-(3-thiotriphosphate) Glutamic Acid Adenosine Triphosphate Trypsin Calcium
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Mehta P P
Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA 92037, USA.
Battenberg E
Wilson M C
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46 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.93.19.10471
Published
1996-09-17
Pages
10471-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC38409
Subset
IM
Grants
NIMH NIH HHS · MH48989 · United States
External Links
PubMed source DOI: 10.1073/pnas.93.19.10471 PMC Full Text View journal details
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