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Journal Article

beta phorbol ester- and diacylglycerol-induced augmentation of transmitter release is mediated by Munc13s and not by PKCs

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Rhee,  J. S.
Department of Membrane Biophysics, MPI for biophysical chemistry, Max Planck Society;

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Rosenmund,  C.
Department of Membrane Biophysics, MPI for biophysical chemistry, Max Planck Society;

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599715.pdf
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Citation

Rhee, J. S., Betz, A., Pyott, S., Reim, K., Varoqueaux, F., Augustin, I., et al. (2002). beta phorbol ester- and diacylglycerol-induced augmentation of transmitter release is mediated by Munc13s and not by PKCs. Cell, 108(1), 121-133. Retrieved from http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6WSN-44XJVN1-F-1&_cdi=7051&_user=38661&_pii=S0092867401006353&_origin=search&_coverDate=01%2F11%2F2002&_sk=998919998&view=c&wchp=dGLzVlb-zSkzS&md5=5ef6f45469f8ab1d3f64a7d7f768d900&ie=/sdarticle.pdf.


Cite as: https://hdl.handle.net/11858/00-001M-0000-0012-F470-A
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.