Synaptotagmin-syntaxin interaction: The C2 domain as a Ca2+-dependent electrostatic switch

Xuguang Shao, Cai Li, Imma Fernandez, Xiangyang Zhang, Thomas C. Südhof, Jose Rizo-Rey

Research output: Contribution to journalArticle

188 Scopus citations

Abstract

Synaptotagmin I is a synaptic vesicle protein that is thought to act as a Ca2+ sensor in neurotransmitter release. The first C2 domain of synaptotagmin I (C2A domain) contains a bipartite Ca2+-binding motif and interacts in a Ca2+-dependent manner with syntaxin, a central component of the membrane fusion complex. Analysis by nuclear magnetic resonance spectroscopy and site-directed mutagenesis shows that this interaction is mediated by the cooperative action of basic residues surrounding the Ca2+- binding sites of the C2A domain and is driven by a change in the electrostatic potential of the C2A domain induced by Ca2+ binding. A model is proposed whereby synaptotagmin acts as an electrostatic switch in Ca2+- triggered synaptic vesicle exocytosis, promoting a structural rearrangement in the fusion machinery that is effected by its interaction with syntaxin.

Original languageEnglish (US)
Pages (from-to)133-142
Number of pages10
JournalNeuron
Volume18
Issue number1
DOIs
StatePublished - Jan 1997

ASJC Scopus subject areas

  • Neuroscience(all)

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