Position of UNC-13 in the active zone regulates synaptic vesicle release probability and release kinetics
Keming Zhou,
Tamara M Stawicki,
Alexandr Goncharov,
Yishi Jin
Affiliations
Keming Zhou
Section of Neurobiology, Division of Biological Sciences, University of California, San Diego, La Jolla, United States
Tamara M Stawicki
Section of Neurobiology, Division of Biological Sciences, University of California, San Diego, La Jolla, United States; Neurosciences Graduate Program, University of California, San Diego, La Jolla, United States
Alexandr Goncharov
Section of Neurobiology, Division of Biological Sciences, University of California, San Diego, La Jolla, United States; Howard Hughes Medical Institute, University of California, San Diego, La Jolla, United States
Yishi Jin
Section of Neurobiology, Division of Biological Sciences, University of California, San Diego, La Jolla, United States; Howard Hughes Medical Institute, University of California, San Diego, La Jolla, United States
The presynaptic active zone proteins UNC-13/Munc13s are essential for synaptic vesicle (SV) exocytosis by directly interacting with SV fusion apparatus. An open question is how their association with active zones, hence their position to Ca2+ entry sites, regulates SV release. The N-termini of major UNC-13/Munc13 isoforms contain a non-calcium binding C2A domain that mediates protein homo- or hetero-meric interactions. Here, we show that the C2A domain of Caenorhabditis elegans UNC-13 regulates release probability of evoked release and its precise active zone localization. Kinetics analysis of SV release supports that the proximity of UNC-13 to Ca2+ entry sites, mediated by the C2A-domain containing N-terminus, is critical for accelerating neurotransmitter release. Additionally, the C2A domain is specifically required for spontaneous release. These data reveal multiple roles of UNC-13 C2A domain, and suggest that spontaneous release and the fast phase of evoked release may involve a common pool of SVs at the active zone.
