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PMID: 20400951 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Nature structural & molecular biology ·Vol. 17 ·No. 5 ·2010-05-00 ·Pages 568-75

Xue M, Craig TK, Xu J, Chao HT, Rizo J, Rosenmund C

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.

MeSH Terms
Adaptor Proteins, Vesicular Transport/chemistry,genetics,metabolism Amino Acid Sequence Animals Calcium/metabolism Cells, Cultured Mice Models, Molecular Molecular Sequence Data Mutation Nerve Tissue Proteins/chemistry,genetics,metabolism Neurons/metabolism Nuclear Magnetic Resonance, Biomolecular Protein Binding Protein Conformation Rats SNARE Proteins/chemistry,metabolism Synaptic Vesicles/metabolism Synaptotagmin I/genetics,metabolism
Chemicals
Adaptor Proteins, Vesicular Transport Nerve Tissue Proteins SNARE Proteins Synaptotagmin I complexin I Calcium
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Xue Mingshan
Department of Neuroscience, Baylor College of Medicine, Houston, Texas, USA.
Craig Timothy K
Xu Junjie
Chao Hsiao-Tuan
Rizo Josep
Rosenmund Christian
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Article Info
Journal
Nature structural & molecular biology
Abbr.
Nat Struct Mol Biol
ISSN
1545-9985
DOI
10.1038/nsmb.1791
Published
2010-05-00
Epub
2010-00-18
Pages
568-75
Language
English
Region
United States
NLM ID
101186374
PMCID
PMC3172005
Subset
IM
Grants
NINDS NIH HHS · R01 NS050655-05 · United States
NINDS NIH HHS · R01 NS037200 · United States
NINDS NIH HHS · R01 NS037200-14 · United States
NIMH NIH HHS · F31MH078678 · United States
NIMH NIH HHS · F31 MH078678 · United States
NINDS NIH HHS · R01 NS050655 · United States
NINDS NIH HHS · NS050655 · United States
NINDS NIH HHS · NS037200 · United States
External Links
PubMed source DOI: 10.1038/nsmb.1791 PMC Full Text View journal details
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