A unique C2 domain at the C terminus of Munc13 promotes synaptic vesicle priming.
Neurotransmitter release during synaptic transmission comprises a tightly orchestrated sequence of molecular events, and Munc13-1 is a cornerstone of the fusion machinery. A forward genetic screen for defects in neurotransmitter release in Caenorhabditis elegans identified a mutation in the Munc13-1 ortholog UNC-13 that eliminated its unique and deeply conserved C-terminal module (referred to as HC2M) containing a Ca2+-insensitive C2 domain flanked by membrane-binding helices. The HC2M module could be functionally replaced in vivo by protein domains that localize to synaptic vesicles but not to the plasma membrane. HC2M is broadly conserved in other Unc13 family members and is required for efficient synaptic vesicle priming. We propose that the HC2M domain evolved as a vesicle/endosome adaptor and acquired synaptic vesicle specificity in the Unc13ABC protein family.
['Padmanarayana|Murugesh|M|0000-0001-5057-9856', 'Liu|Haowen|H|0000-0001-8498-290X', 'Michelassi|Francesco|F|', 'Li|Lei|L|0000-0002-6062-7097', 'Betensky|Daniel|D|', 'Dominguez|Matthew J|MJ|0000-0003-1033-5181', 'Sutton|R Bryan|RB|0000-0001-8393-5239', 'Hu|Zhitao|Z|0000-0002-2948-3339', 'Dittman|Jeremy S|JS|0000-0002-3850-9078']
D000595:Amino Acid Sequence D000818:Animals D017173:Caenorhabditis elegans D029742:Caenorhabditis elegans Proteins D005089:Exocytosis D008565:Membrane Proteins D009154:Mutation D009419:Nerve Tissue Proteins D018377:Neurotransmitter Agents D000072417:Protein Domains D017384:Sequence Deletion D009435:Synaptic Transmission D013572:Synaptic Vesicles
C2 Munc13 synaptic vesicle Caenorhabditis elegans unc-13