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Publication : Molecular Mechanisms of Synaptic Vesicle Priming by Munc13 and Munc18.

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.
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