Cell
Volume 108, Issue 1, 11 January 2002, Pages 121-133
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Article
β Phorbol Ester- and Diacylglycerol-Induced Augmentation of Transmitter Release Is Mediated by Munc13s and Not by PKCs

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Abstract

Munc13-1 is a presynaptic protein with an essential role in synaptic vesicle priming. It contains a diacylglycerol (DAG)/β phorbol ester binding C1 domain and is a potential target of the DAG second messenger pathway that may act in parallel with PKCs. Using genetically modified mice that express a DAG/β phorbol ester binding-deficient Munc13-1H567K variant instead of the wild-type protein, we determined the relative contribution of PKCs and Munc13-1 to DAG/β phorbol ester-dependent regulation of neurotransmitter release. We show that Munc13s are the main presynaptic DAG/β phorbol ester receptors in hippocampal neurons. Modulation of Munc13-1 activity by second messengers via the DAG/β phorbol ester binding C1 domain is essential for use-dependent alterations of synaptic efficacy and survival.

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These authors contributed equally to this work.

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Present address: Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544.

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Correspondence: Nils Brose, 49-551-3899725 (phone), 49-551-3899753 (fax), e-mail: [email protected]; Christian Rosenmund, 49-551-2011672 (phone), 49-551-2011688 (fax), e-mail: [email protected]