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Synaptotagmin activates membrane fusion through a Ca-dependent trans interaction with phospholipids

Nature Structural and Molecular Biology, ISSN: 1545-9993, Vol: 14, Issue: 10, Page: 904-911
2007
  • 139
    Citations
  • 0
    Usage
  • 138
    Captures
  • 2
    Mentions
  • 0
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    139
  • Captures
    138
  • Mentions
    2
    • News Mentions
      1
      • 1
    • References
      1
      • 1

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Article Description

Synaptotagmin-1 is the calcium sensor for neuronal exocytosis, but the mechanism by which it triggers membrane fusion is not fully understood. Here we show that synaptotagmin accelerates SNARE-dependent fusion of liposomes by interacting with neuronal Q-SNARES in a Ca-independent manner. Ca-dependent binding of synaptotagmin to its own membrane impedes the activation. Preventing this cis interaction allows Ca to trigger synaptotagmin binding in trans, accelerating fusion. However, when an activated SNARE acceptor complex is used, synaptotagmin has no effect on fusion kinetics, suggesting that synaptotagmin operates upstream of SNARE assembly in this system. Our results resolve major discrepancies concerning the effects of full-length synaptotagmin and its C2AB fragment on liposome fusion and shed new light on the interactions of synaptotagmin with SNAREs and membranes. However, our findings also show that the action of synaptotagmin on the fusion-arrested state of docked vesicles in vivo is not fully reproduced in vitro. © 2007 Nature Publishing Group.

Bibliographic Details

Stein, Alexander; Radhakrishnan, Anand; Riedel, Dietmar; Fasshauer, Dirk; Jahn, Reinhard

Springer Science and Business Media LLC

Biochemistry, Genetics and Molecular Biology

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