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Proc Natl Acad Sci U S A. 2013 Sep 10;110(37):15079-84. doi: 10.1073/pnas.1314427110. Epub 2013 Aug 26.

Superpriming of synaptic vesicles after their recruitment to the readily releasable pool.

Author information

1
Cell Physiology Laboratory, Department of Physiology and Bio-Membrane Plasticity Research Center, Seoul National University College of Medicine and Neuroscience Research Institute, Seoul National University Medical Research Center, Seoul 110-799, Republic of Korea.

Abstract

Recruitment of release-competent vesicles during sustained synaptic activity is one of the major factors governing short-term plasticity. During bursts of synaptic activity, vesicles are recruited to a fast-releasing pool from a reluctant vesicle pool through an actin-dependent mechanism. We now show that newly recruited vesicles in the fast-releasing pool do not respond at full speed to a strong Ca(2+) stimulus, but require approximately 4 s to mature to a "superprimed" state. Superpriming was found to be altered by agents that modulate the function of unc13 homolog proteins (Munc13s), but not by calmodulin inhibitors or actin-disrupting agents. These findings indicate that recruitment and superpriming of vesicles are regulated by separate mechanisms, which require integrity of the cytoskeleton and activation of Munc13s, respectively. We propose that refilling of the fast-releasing vesicle pool proceeds in two steps, rapid actin-dependent "positional priming," which brings vesicles closer to Ca(2+) sources, followed by slower superpriming, which enhances the Ca(2+) sensitivity of primed vesicles.

KEYWORDS:

calyx of Held; diacylglycerol; phospholipase C; presynaptic; vesicle release rate constant

PMID:
23980146
PMCID:
PMC3773744
DOI:
10.1073/pnas.1314427110
[Indexed for MEDLINE]
Free PMC Article
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