Article abstract
Nature Structural & Molecular Biology 15, 827 - 835 (2008)
Published online: 11 July 2008 | doi:10.1038/nsmb.1463
Synaptotagmin arrests the SNARE complex before triggering fast, efficient membrane fusion in response to Ca2+
Michael C Chicka1,2, Enfu Hui1, Huisheng Liu1 & Edwin R Chapman1
Abstract
Neuronal communication is mediated by Ca2+-triggered fusion of transmitter-filled synaptic vesicles with the presynaptic plasma membrane. Synaptotagmin I functions as a Ca2+ 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 Ca2+ 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 Ca2+, drive rapid, highly efficient lipid mixing. Ca2+-independent interactions with SNAREs also predispose synaptotagmin to selectively penetrate the target membrane in response to Ca2+; we demonstrate that Ca2+–synaptotagmin must insert into the target membrane to accelerate SNARE-catalyzed fusion. These findings demonstrate that Ca2+ converts synaptotagmin from a clamp to a trigger for exocytosis.
- Howard Hughes Medical Institute and Department of Physiology, University of Wisconsin, Madison, 1300 University Avenue, SMI 129, Madison, Wisconsin 53706, USA.
- Graduate Program in Cellular and Molecular Biology, University of Wisconsin, Madison, 1300 University Avenue, SMI 129, Madison, Wisconsin 53706, USA.
Correspondence to: Edwin R Chapman1 e-mail: chapman@physiology.wisc.edu
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