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Elife. 2014 Feb 11;3:e01715. doi: 10.7554/eLife.01715.

Munc18-1 is a dynamically regulated PKC target during short-term enhancement of transmitter release.

Author information

1
Laboratory of Synaptic Mechanisms, Brain Mind Institute, School of Life Science, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.

Abstract

Transmitter release at synapses is regulated by preceding neuronal activity, which can give rise to short-term enhancement of release like post-tetanic potentiation (PTP). Diacylglycerol (DAG) and Protein-kinase C (PKC) signaling in the nerve terminal have been widely implicated in the short-term modulation of transmitter release, but the target protein of PKC phosphorylation during short-term enhancement has remained unknown. Here, we use a gene-replacement strategy at the calyx of Held, a large CNS model synapse that expresses robust PTP, to study the molecular mechanisms of PTP. We find that two PKC phosphorylation sites of Munc18-1 are critically important for PTP, which identifies the presynaptic target protein for the action of PKC during PTP. Pharmacological experiments show that a phosphatase normally limits the duration of PTP, and that PTP is initiated by the action of a 'conventional' PKC isoform. Thus, a dynamic PKC phosphorylation/de-phosphorylation cycle of Munc18-1 drives short-term enhancement of transmitter release during PTP. DOI: http://dx.doi.org/10.7554/eLife.01715.001.

KEYWORDS:

calyx of Held; protein kinase C; protein phosphatase; synaptic plasticity; synaptic transmission; transmitter release

PMID:
24520164
PMCID:
PMC3919271
DOI:
10.7554/eLife.01715
[Indexed for MEDLINE]
Free PMC Article

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