Beta phorbol ester- and diacylglycerol-induced augmentation of transmitter release is mediated by Munc13s and not by PKCs. |
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| Authors: | Jeong Seop Rhee Andrea Betz Sonja Pyott Kerstin Reim Frederique Varoqueaux Iris Augustin D?rte Hesse Thomas C Südhof Masami Takahashi Christian Rosenmund Nils Brose |
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| Affiliation: | Abteilung Membranbiophysik, Max-Planck-Institut für Biophysikalische Chemie, Am Fassberg 11, D-37077 G?ttingen, Bundesrepublik Deutschland. |
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| Abstract: | Munc13-1 is a presynaptic protein with an essential role in synaptic vesicle priming. It contains a diacylglycerol (DAG)/beta phorbol ester binding C(1) 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/beta phorbol ester binding-deficient Munc13-1(H567K) variant instead of the wild-type protein, we determined the relative contribution of PKCs and Munc13-1 to DAG/beta phorbol ester-dependent regulation of neurotransmitter release. We show that Munc13s are the main presynaptic DAG/beta phorbol ester receptors in hippocampal neurons. Modulation of Munc13-1 activity by second messengers via the DAG/beta phorbol ester binding C(1) domain is essential for use-dependent alterations of synaptic efficacy and survival. |
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