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

2012/03/23

Meijer M, Burkhardt P, de Wit H, Toonen RF, Fasshauer D, Verhage M.

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


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.

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