First Author | Lai Y | Year | 2017 |
Journal | Neuron | Volume | 95 |
Issue | 3 | Pages | 591-607.e10 |
PubMed ID | 28772123 | Mgi Jnum | J:256119 |
Mgi Id | MGI:6114574 | Doi | 10.1016/j.neuron.2017.07.004 |
Citation | Lai Y, et al. (2017) Molecular Mechanisms of Synaptic Vesicle Priming by Munc13 and Munc18. Neuron 95(3):591-607.e10 |
abstractText | Munc13 catalyzes the transit of syntaxin from a closed complex with Munc18 into the ternary SNARE complex. Here we report a new function of Munc13, independent of Munc18: it promotes the proper syntaxin/synaptobrevin subconfiguration during assembly of the ternary SNARE complex. In cooperation with Munc18, Munc13 additionally ensures the proper syntaxin/SNAP-25 subconfiguration. In a reconstituted fusion assay with SNAREs, complexin, and synaptotagmin, inclusion of both Munc13 and Munc18 quadruples the Ca(2+)-triggered amplitude and achieves Ca(2+) sensitivity at near-physiological concentrations. In Munc13-1/2 double-knockout neurons, expression of a constitutively open mutant of syntaxin could only minimally restore neurotransmitter release relative to Munc13-1 rescue. Together, the physiological functions of Munc13 may be related to regulation of proper SNARE complex assembly. |