The trans-SNARE-regulating function of Munc18-1 is essential to synaptic exocytosis.

ABSTRACT: The fusion of neurotransmitter-filled synaptic vesicles with the plasma membrane requires two classes of molecules-SNAP receptor (SNARE) and Sec1/Munc18 (SM) protein. Reconstitution studies suggest that the SM protein Munc18-1 promotes the zippering of trans-SNARE complexes and accelerates the kinetics of SNARE-dependent membrane fusion. However, the physiological role of this trans-SNARE-regulating function in synaptic exocytosis remains to be established. Here we first demonstrate that two mutations in the vesicle-anchored v-SNARE selectively impair the ability of Munc18-1 to promote trans-SNARE zippering, whereas other known Munc18-1/SNARE-binding modes are unaffected. In cultured neurons, these v-SNARE mutations strongly inhibit spontaneous as well as evoked neurotransmitter release, p

SUBMITTER: Shen C 

PROVIDER: S-EPMC4668942 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature