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

Marieke Meijer, Pawel Burkhardt, Heidi de Wit, Ruud F Toonen, Dirk Fasshauer, Matthijs Verhage

The EMBO journal 2012 May 02

filter terms:

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.

Citation

Marieke Meijer, Pawel Burkhardt, Heidi de Wit, Ruud F Toonen, Dirk Fasshauer, Matthijs Verhage. Munc18-1 mutations that strongly impair SNARE-complex binding support normal synaptic transmission. The EMBO journal. 2012 May 02;31(9):2156-68