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EMBO J. 2012 May 2;31(9):2156-68. doi: 10.1038/emboj.2012.72. Epub 2012 Mar 23.

Munc18-1 mutations that strongly impair SNARE-complex binding support normal synaptic transmission.

Author information

1
Department of Functional Genomics and Department of Clinical Genetics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University Amsterdam, The Netherlands.

Abstract

Synaptic transmission depends critically on the Sec1p/Munc18 protein Munc18-1, but it is unclear whether Munc18-1 primarily operates as a integral part of the fusion machinery or has a more upstream role in fusion complex assembly. Here, we show that point mutations in Munc18-1 that interfere with binding to the free Syntaxin1a N-terminus and strongly impair binding to assembled SNARE complexes all support normal docking, priming and fusion of synaptic vesicles, and normal synaptic plasticity in munc18-1 null mutant neurons. These data support a prevailing role of Munc18-1 before/during SNARE-complex assembly, while its continued association to assembled SNARE complexes is dispensable for synaptic transmission.

PMID:
22446389
PMCID:
PMC3343470
DOI:
10.1038/emboj.2012.72
[Indexed for MEDLINE]
Free PMC Article

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