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PMID: 18622390 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Synaptotagmin arrests the SNARE complex before triggering fast, efficient membrane fusion in response to Ca2+.

Nature structural & molecular biology ·Vol. 15 ·No. 8 ·2008-08-00 ·Pages 827-35

Chicka MC, Hui E, Liu H, Chapman ER

Abstract

Neuronal communication is mediated by Ca(2+)-triggered fusion of transmitter-filled synaptic vesicles with the presynaptic plasma membrane. Synaptotagmin I functions as a Ca(2+) sensor that regulates exocytosis, whereas soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptor (SNARE) proteins in the vesicle and target membrane assemble into complexes that directly catalyze bilayer fusion. Here we report that, before the Ca(2+) trigger, synaptotagmin interacts with SNARE proteins in the target membrane to halt SNARE complex assembly at a step after donor vesicles attach, or dock, to target membranes. This results in fusion complexes that, when subsequently triggered by Ca(2+), drive rapid, highly efficient lipid mixing. Ca(2+)-independent interactions with SNAREs also predispose synaptotagmin to selectively penetrate the target membrane in response to Ca(2+); we demonstrate that Ca(2+)-synaptotagmin must insert into the target membrane to accelerate SNARE-catalyzed fusion. These findings demonstrate that Ca(2+) converts synaptotagmin from a clamp to a trigger for exocytosis.

MeSH Terms
Animals Calcium/metabolism Catalysis Cell Membrane/metabolism Electrophysiology Exocytosis Hippocampus/metabolism Lipids/chemistry Mice Mice, Knockout Models, Biological Plasmids/metabolism Rats SNARE Proteins/metabolism Synaptotagmins/metabolism,physiology
Chemicals
Lipids SNARE Proteins Synaptotagmins Calcium
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Chicka Michael C
Howard Hughes Medical Institute and Department of Physiology, University of Wisconsin, Madison, 1300 University Avenue, SMI 129, Madison, Wisconsin 53706, USA.
Hui Enfu
Liu Huisheng
Chapman Edwin R
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Article Info
Journal
Nature structural & molecular biology
Abbr.
Nat Struct Mol Biol
ISSN
1545-9985
DOI
10.1038/nsmb.1463
Published
2008-08-00
Epub
2008-00-11
Pages
827-35
Language
English
Region
United States
NLM ID
101186374
PMCID
PMC2570314
Subset
IM
Grants
NIGMS NIH HHS · R01 GM056827-09 · United States
Howard Hughes Medical Institute · United States
NIMH NIH HHS · R01 MH061876-06 · United States
NIGMS NIH HHS · R01 GM056827 · United States
NIMH NIH HHS · R01 MH061876 · United States
External Links
PubMed source DOI: 10.1038/nsmb.1463 PMC Full Text View journal details
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