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

Mingshan Xue, Timothy K. Craig, Junjie Xu, Hsiao Tuan Chao, Jose Rizo-Rey, Christian Rosenmund

Research output: Contribution to journalArticle

74 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)568-575
Number of pages8
JournalNature Structural and Molecular Biology
Volume17
Issue number5
DOIs
StatePublished - May 2010

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Synaptotagmin I
SNARE Proteins
Synaptic Vesicles
Exocytosis
Neurotransmitter Agents
Neurons
Proteins

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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Binding of the complexin N terminus to the SNARE complex potentiates synaptic-vesicle fusogenicity. / Xue, Mingshan; Craig, Timothy K.; Xu, Junjie; Chao, Hsiao Tuan; Rizo-Rey, Jose; Rosenmund, Christian.

In: Nature Structural and Molecular Biology, Vol. 17, No. 5, 05.2010, p. 568-575.

Research output: Contribution to journalArticle

Xue, Mingshan ; Craig, Timothy K. ; Xu, Junjie ; Chao, Hsiao Tuan ; Rizo-Rey, Jose ; Rosenmund, Christian. / Binding of the complexin N terminus to the SNARE complex potentiates synaptic-vesicle fusogenicity. In: Nature Structural and Molecular Biology. 2010 ; Vol. 17, No. 5. pp. 568-575.
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