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- W1969841566 abstract "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." @default.
- W1969841566 created "2016-06-24" @default.
- W1969841566 creator A5013505487 @default.
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- W1969841566 date "2009-03-02" @default.
- W1969841566 modified "2023-10-14" @default.
- W1969841566 title "Munc18-1 binding to the neuronal SNARE complex controls synaptic vesicle priming" @default.
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- W1969841566 doi "https://doi.org/10.1083/jcb.200812026" @default.
- W1969841566 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2686405" @default.
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