Article abstract
Nature Structural & Molecular Biology 14, 904 - 911 (2007)
Published online: 23 September 2007 | doi:10.1038/nsmb1305
Synaptotagmin activates membrane fusion through a Ca2+-dependent trans interaction with phospholipids
Alexander Stein1, Anand Radhakrishnan1, Dietmar Riedel1, Dirk Fasshauer1 & Reinhard Jahn1
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.
- Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, D-37077 Göttingen, Germany.
Correspondence to: Reinhard Jahn1 e-mail: rjahn@gwdg.de
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
NEWS AND VIEWS
Membrane fusion SNAREs line up in new environmentNature News and Views (07 May 1998)
Synaptotagmin: fusogenic role for calcium sensor?Nature Structural & Molecular Biology News and Views (01 Apr 2006)
See all 7 matches for News And ViewsRESEARCH
Post-phosphorylation prolyl isomerisation of gephyrin represents a mechanism to modulate glycine receptors functionThe EMBO Journal Article (04 Apr 2007)
Ca 2+ ?synaptotagmin directly regulates t-SNARE function during reconstituted membrane fusionNature Structural & Molecular Biology Article (01 Apr 2006)
See all 60 matches for Research
