Ca2+-dependent synaptotagmin binding to SNAP-25 is essential for Ca2+-triggered exocytosis

Xiaodong Zhang, Mindy J. Kim-Miller, Mitsunori Fukuda, Judith A. Kowalchyk, Thomas F.J. Martin

Research output: Contribution to journalArticlepeer-review

195 Citations (Scopus)

Abstract

Synaptotagmin is a proposed Ca2+ sensor on the vesicle for regulated exocytosis and exhibits Ca2+-dependent binding to phospholipids, syntaxin, and SNAP-25 in vitro, but the mechanism by which Ca2+ triggers membrane fusion is uncertain. Previous studies suggested that SNAP-25 plays a role in the Ca2+ regulation of secretion. We found that synaptotagmins I and IX associate with SNAP-25 during Ca2+-dependent exocytosis in PC12 cells, and we identified C-terminal amino acids in SNAP-25 (Asp179, Asp186, Asp193) that are required for Ca2+-dependent synaptotagmin binding. Replacement of SNAP-25 in PC12 cells with SNAP-25 containing C-terminal Asp mutations led to a loss-of-function in regulated exocytosis at the Ca2+-dependent fusion step. These results indicate that the Ca2+-dependent interaction of synaptotagmin with SNAP-25 is essential for the Ca2+-dependent triggering of membrane fusion.

Original languageEnglish
Pages (from-to)599-611
Number of pages13
JournalNeuron
Volume34
Issue number4
DOIs
Publication statusPublished - 2002 May 16
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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