Position of UNC-13 in the active zone regulates synaptic vesicle release probability and release kinetics.
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 Ca(2+) 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 Ca(2+) 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. DOI: http://dx.doi.org/10.7554/eLife.01180.001.
Section of Neurobiology, Division of Biological Sciences, University of California, San Diego, La Jolla, United States.
Keming
K
Zhou
Tamara M
TM
Stawicki
Alexandr
A
Goncharov
Yishi
Y
Jin
D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D007700:Kinetics; D009154:Mutation; D013572:Synaptic Vesicles / Q000378:metabolism*
D002352:Carrier Proteins; C083141:phorbol ester binding protein
C2A domain; Chromophore assisted light inactivation; Munc-13; SV release kinetics; SV release probability; UNC-13; miniSOG