RGD Reference Report - Munc18-1 binding to the neuronal SNARE complex controls synaptic vesicle priming. - Rat Genome Database

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Munc18-1 binding to the neuronal SNARE complex controls synaptic vesicle priming.

Authors: Deak, F  Xu, Y  Chang, WP  Dulubova, I  Khvotchev, M  Liu, X  Sudhof, TC  Rizo, J 
Citation: Deak F, etal., J Cell Biol. 2009 Mar 9;184(5):751-64. Epub 2009 Mar 2.
RGD ID: 2311128
Pubmed: (View Article at PubMed) PMID:19255244
DOI: Full-text: DOI:10.1083/jcb.200812026

Munc18-1 and soluble NSF attachment protein receptors (SNAREs) are critical for synaptic vesicle fusion. Munc18-1 binds to the SNARE syntaxin-1 folded into a closed conformation and to SNARE complexes containing open syntaxin-1. Understanding which steps in fusion depend on the latter interaction and whether Munc18-1 competes with other factors such as complexins for SNARE complex binding is critical to elucidate the mechanisms involved. In this study, we show that lentiviral expression of Munc18-1 rescues abrogation of release in Munc18-1 knockout mice. We describe point mutations in Munc18-1 that preserve tight binding to closed syntaxin-1 but markedly disrupt Munc18-1 binding to SNARE complexes containing open syntaxin-1. Lentiviral rescue experiments reveal that such disruption selectively impairs synaptic vesicle priming but not Ca(2+)-triggered fusion of primed vesicles. We also find that Munc18-1 and complexin-1 bind simultaneously to SNARE complexes. These results suggest that Munc18-1 binding to SNARE complexes mediates synaptic vesicle priming and that the resulting primed state involves a Munc18-1-SNARE-complexin macromolecular assembly that is poised for Ca(2+) triggering of fusion.

Annotation

Gene Ontology Annotations    

Biological Process

Cellular Component

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Cplx1  (complexin 1)
Stx1a  (syntaxin 1A)
Stxbp1  (syntaxin binding protein 1)


Additional Information