Binding of the complexin N terminus to the SNARE complex potentiates synaptic-vesicle fusogenicity.
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.
Xue
Mingshan
M
Department of Neuroscience, Baylor College of Medicine, Houston, Texas, USA.
Craig
Timothy K
TK
Xu
Junjie
J
Chao
Hsiao-Tuan
HT
Rizo
Josep
J
Rosenmund
Christian
C
D033942:Adaptor Proteins, Vesicular Transport / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D011487:Protein Conformation; D051381:Rats; D050600:SNARE Proteins / Q000737:chemistry / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000378:metabolism*; D050863:Synaptotagmin I / Q000235:genetics / Q000378:metabolism
D033942:Adaptor Proteins, Vesicular Transport; D009419:Nerve Tissue Proteins; D050600:SNARE Proteins; D050863:Synaptotagmin I; C095992:complexin I; D002118:Calcium
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