Synaptotagmin activates membrane fusion through a Ca2+-dependent trans interaction with phospholipids.

Details

Serval ID
serval:BIB_39F3160D4524
Type
Article: article from journal or magazin.
Collection
Publications
Title
Synaptotagmin activates membrane fusion through a Ca2+-dependent trans interaction with phospholipids.
Journal
Nature Structural and Molecular Biology
Author(s)
Stein A., Radhakrishnan A., Riedel D., Fasshauer D., Jahn R.
ISSN
1545-9993 (Print)
ISSN-L
1545-9985
Publication state
Published
Issued date
2007
Peer-reviewed
Oui
Volume
14
Number
10
Pages
904-911
Language
english
Abstract
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 Ca2+-independent manner. Ca2+-dependent binding of synaptotagmin to its own membrane impedes the activation. Preventing this cis interaction allows Ca2+ 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.
Keywords
Animals, Calcium/metabolism, Liposomes/metabolism, Membrane Fusion/physiology, Multiprotein Complexes, Neurons/metabolism, Peptide Fragments/genetics, Peptide Fragments/metabolism, Phospholipids/metabolism, Rats, SNARE Proteins/metabolism, Synaptotagmin I/genetics, Synaptotagmin I/metabolism
Pubmed
Web of science
Create date
15/09/2011 8:10
Last modification date
20/08/2019 13:29
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