Abstract
Ca2+ binding to synaptotagmin 1 triggers fast exocytosis of synaptic vesicles that have been primed for release by SNARE-complex assembly. Besides synaptotagmin 1, fast Ca2+-triggered exocytosis requires complexins. Synaptotagmin 1 and complexins both bind to assembled SNARE complexes, but it is unclear how their functions are coupled. Here we propose that complexin binding activates SNARE complexes into a metastable state and that Ca2+ binding to synaptotagmin 1 triggers fast exocytosis by displacing complexin from metastable SNARE complexes. Specifically, we demonstrate that, biochemically, synaptotagmin 1 competes with complexin for SNARE-complex binding, thereby dislodging complexin from SNARE complexes in a Ca2+-dependent manner. Physiologically, increasing the local concentration of complexin selectively impairs fast Ca2+-triggered exocytosis but retains other forms of SNARE-dependent fusion. The hypothesis that Ca2+-induced displacement of complexins from SNARE complexes triggers fast exocytosis accounts for the loss-of-function and gain-of-function phenotypes of complexins and provides a molecular explanation for the high speed and synchronicity of fast Ca2+-triggered neurotransmitter release.
Original language | English (US) |
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Pages (from-to) | 1175-1187 |
Number of pages | 13 |
Journal | Cell |
Volume | 126 |
Issue number | 6 |
DOIs | |
State | Published - Sep 22 2006 |
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)