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Elife. 2013 Nov 12;2:e01180. doi: 10.7554/eLife.01180.

Position of UNC-13 in the active zone regulates synaptic vesicle release probability and release kinetics.

Author information

1
Section of Neurobiology, Division of Biological Sciences, University of California, San Diego, La Jolla, United States.

Abstract

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.

KEYWORDS:

C2A domain; Chromophore assisted light inactivation; Munc-13; SV release kinetics; SV release probability; UNC-13; miniSOG

PMID:
24220508
PMCID:
PMC3821175
DOI:
10.7554/eLife.01180
[Indexed for MEDLINE]
Free PMC Article

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