A unique C2 domain at the C terminus of Munc13 promotes synaptic vesicle priming

作者: Jeremy S. Dittman , Murugesh Padmanarayana , R. Bryan Sutton , Zhitao Hu , Matthew J. Dominguez

DOI: 10.1073/PNAS.2016276118

关键词: Protein familyC2 domainSynaptic vesicle primingCell biologyNeurotransmitterChemistryProtein domainVesicleSynaptic vesicleNeurotransmission

摘要: Neurotransmitter release during synaptic transmission comprises a tightly orchestrated sequence of molecular events, and Munc13-1 is cornerstone the fusion machinery. A forward genetic screen for defects in neurotransmitter Caenorhabditis elegans identified mutation ortholog UNC-13 that eliminated its unique deeply conserved C-terminal module (referred to as HC2M) containing Ca2+-insensitive C2 domain flanked by membrane-binding helices. The HC2M could be functionally replaced vivo protein domains localize vesicles but not plasma membrane. broadly other Unc13 family members required efficient vesicle priming. We propose evolved vesicle/endosome adaptor acquired specificity Unc13ABC family.

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