Abstract
Complexins facilitate and inhibit neurotransmitter release through distinct domains, and their function was proposed to be coupled to the Ca 2+ 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 Ca 2+-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.
Original language | English (US) |
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Pages (from-to) | 568-575 |
Number of pages | 8 |
Journal | Nature Structural and Molecular Biology |
Volume | 17 |
Issue number | 5 |
DOIs | |
State | Published - May 2010 |
ASJC Scopus subject areas
- Structural Biology
- Molecular Biology