Close membrane-membrane proximity induced by Ca2+-dependent multivalent binding of synaptotagmin-1 to phospholipids

Demet Araç, Xiaocheng Chen, Htet A. Khant, Josep Ubach, Steven J. Ludtke, Masahide Kikkawa, Arthur E. Johnson, Wah Chiu, Thomas C. Südhof, Jose Rizo-Rey

Research output: Contribution to journalArticle

184 Scopus citations

Abstract

Synaptotagmin acts as a Ca2+ sensor in neurotransmitter release through its two C2 domains. Ca2+-dependent phospholipid binding is key for synaptotagmin function, but it is unclear how this activity cooperates with the SNARE complex involved in release or why Ca2+ binding to the C2B domain is more crucial for release than Ca 2+ binding to the C2A domain. Here we show that Ca 2+ induces high-affinity simultaneous binding of synaptotagmin to two membranes, bringing them into close proximity. The synaptotagmin C2B domain is sufficient for this ability, which arises from the abundance of basic residues around its surface. We propose a model wherein synaptotagmin cooperates with the SNAREs in bringing the synaptic vesicle and plasma membranes together and accelerates membrane fusion through the highly positive electrostatic potential of its C2B domain.

Original languageEnglish (US)
Pages (from-to)209-217
Number of pages9
JournalNature Structural and Molecular Biology
Volume13
Issue number3
DOIs
StatePublished - Mar 1 2006

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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    Araç, D., Chen, X., Khant, H. A., Ubach, J., Ludtke, S. J., Kikkawa, M., Johnson, A. E., Chiu, W., Südhof, T. C., & Rizo-Rey, J. (2006). Close membrane-membrane proximity induced by Ca2+-dependent multivalent binding of synaptotagmin-1 to phospholipids. Nature Structural and Molecular Biology, 13(3), 209-217. https://doi.org/10.1038/nsmb1056