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 maj...

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Bibliographic Details
Published in:eLife 2013-11, Vol.2, p.e01180-e01180
Main Authors: Zhou, Keming, Stawicki, Tamara M, Goncharov, Alexandr, Jin, Yishi
Format: Article
Language:English
Subjects:
Animals
C2A domain
Caenorhabditis elegans - metabolism
Calcium
Calcium influx
Carrier Proteins - genetics
Carrier Proteins - metabolism
Carrier Proteins - physiology
Exocytosis
Genotype & phenotype
Isoforms
Kinetics
Light
Localization
miniSOG
Munc-13
Mutation
N-Terminus
Neuroscience
Neurosciences
Neurotransmitter release
Proteins
Sucrose
SV release kinetic
SV release probability
Synaptic Vesicles - metabolism
UNC-13
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Summary: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.
ISSN:2050-084X
2050-084X
DOI:10.7554/elife.01180