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

Mingshan Xue; Craig, Timothy K.; Junjie Xu; Chao, Hsiao-Tuan; Rizo, Josep; Rosenmund, Christian
May 2010
Nature Structural & Molecular Biology;May2010, Vol. 17 Issue 5, p568
Academic Journal
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.


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