SNAREpin Assembly by Munc18-1 Requires Previous Vesicle Docking by Synaptotagmin 1

Regulated exocytosis requires the general membrane fusion machinery-soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) and Sec1/Munc18 (SM) proteins. Using reconstituted giant unilamellar vesicles containing preassembled t-SNARE proteins (syntaxin 1·SNAP-25), we determined...

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Main Authors: Parisotto, Daniel (Author) , Malsam, Jörg (Author) , Malsam, Andrea (Author) , Krause, Jean Michel (Author) , Söllner, Thomas (Author)
Format: Article (Journal)
Language:English
Published: 2012
In: The journal of biological chemistry
Year: 2012, Volume: 287, Issue: 37, Pages: 31041-31049
ISSN:1083-351X
DOI:10.1074/jbc.M112.386805
Online Access:Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1074/jbc.M112.386805
Verlag, kostenfrei, Volltext: http://www.jbc.org/content/287/37/31041
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Author Notes:Daniel Parisotto, Jörg Malsam, Andrea Scheutzow, Jean Michel Krause, Thomas H. Söllner
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Summary:Regulated exocytosis requires the general membrane fusion machinery-soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) and Sec1/Munc18 (SM) proteins. Using reconstituted giant unilamellar vesicles containing preassembled t-SNARE proteins (syntaxin 1·SNAP-25), we determined how Munc18-1 controls the docking, priming, and fusion of small unilamellar vesicles containing the v-SNARE VAMP2 and the Ca2+ sensor synaptotagmin 1. In vitro assays allowed us to position Munc18-1 in the center of a sequential reaction cascade; vesicle docking by synaptotagmin 1 is a prerequisite for Munc18-1 to accelerate trans-SNARE complex (SNAREpin) assembly and membrane fusion. Complexin II stalls SNAREpin zippering at a late stage and, hence, contributes to synchronize membrane fusion in a Ca2+- and synaptotagmin 1-dependent manner. Thus, at the neuronal synapse, the priming factor Munc18-1 may accelerate the conversion of docked synaptic vesicles into a readily releasable pool by activating SNAREs for efficient membrane fusion.
Item Description:First published on July 18, 2012
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Physical Description:Online Resource
ISSN:1083-351X
DOI:10.1074/jbc.M112.386805