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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Zhang, X; Kim-Miller, MJ; Fukuda, M; Kowalchyk, JA; Martin, TFJ

Published Date

  • May 16, 2002

Published In

Volume / Issue

  • 34 / 4

Start / End Page

  • 599 - 611

PubMed ID

  • 12062043

Pubmed Central ID

  • 12062043

International Standard Serial Number (ISSN)

  • 0896-6273

Digital Object Identifier (DOI)

  • 10.1016/s0896-6273(02)00671-2

Language

  • eng

Conference Location

  • United States