A Complexin/Synaptotagmin 1 Switch Controls Fast Synaptic Vesicle Exocytosis

Jiong Tang, Anton Maximov, Ok Ho Shin, Han Dai, Jose Rizo-Rey, Thomas C. Südhof

Research output: Contribution to journalArticlepeer-review

318 Scopus citations

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 languageEnglish (US)
Pages (from-to)1175-1187
Number of pages13
JournalCell
Volume126
Issue number6
DOIs
StatePublished - Sep 22 2006

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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