TITLE

Binding of the complexin N terminus to the SNARE complex potentiates synaptic-vesicle fusogenicity

AUTHOR(S)
Mingshan Xue; Craig, Timothy K.; Junjie Xu; Chao, Hsiao-Tuan; Rizo, Josep; Rosenmund, Christian
PUB. DATE
May 2010
SOURCE
Nature Structural & Molecular Biology;May2010, Vol. 17 Issue 5, p568
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Complexins facilitate and inhibit neurotransmitter release through distinct domains, and their function was proposed to be coupled to the Ca2+ sensor synaptotagmin-1 (Syt1). However, the mechanisms underlying complexin function remain unclear. We now uncover an interaction between the complexin N terminus and the SNARE complex C terminus, and we show that disrupting this interaction abolishes the facilitatory function of complexins in mouse neurons. Analyses of hypertonically induced exocytosis show that complexins enhance synaptic-vesicle fusogenicity. Genetic experiments crossing complexin- and Syt1-null mice indicate a functional interaction between these proteins but also show that complexins can promote Ca2+-triggered release in the absence of Syt1. We propose that the complexin N terminus stabilizes the SNARE complex C terminus and/or helps release the inhibitory function of complexins, thereby activating the fusion machinery in a manner that may cooperate with Syt1 but does not require Syt1.
ACCESSION #
50249294

 

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