Munc13-1 Is a Presynaptic Phorbol Ester Receptor that Enhances Neurotransmitter Release

• Published in: Neuron (Cambridge, Mass.) Vol. 21; no. 1; pp. 123 - 136
• Main Authors: Betz, Andrea, Ashery, Uri, Rickmann, Michael, Augustin, Iris, Neher, Erwin, Südhof, Thomas C, Rettig, Jens, Brose, Nils
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.1998
• Subjects: Amino Acid Sequence; Animals; Biological Transport - drug effects; Brain - metabolism; Caenorhabditis elegans Proteins; Carrier Proteins; Cell Line; diacylglycerol; Female; Humans; Molecular Sequence Data; Munc13-1 protein; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Nerve Tissue Proteins - physiology; Neuromuscular Junction - metabolism; Neurotransmitter Agents - metabolism; Phorbol Esters - metabolism; Phorbol Esters - pharmacology; Presynaptic Terminals - metabolism; Protein Kinase C - metabolism; Rats; Rats, Sprague-Dawley; Receptors, Drug - metabolism; Synaptic Transmission - physiology; Tissue Distribution; Xenopus - metabolism
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/S0896-6273(00)80520-6

Munc13-1, a mammalian homolog of C. elegans unc-13p, is thought to be involved in the regulation of synaptic transmission. We now demonstrate that Munc13-1 is a presynaptic high-affinity phorbol ester and diacylglycerol receptor with ligand affinities similar to those of protein kinase C. Munc13-1 associates with the plasma membrane in response to phorbol ester binding and acts as a phorbol ester–dependent enhancer of transmitter release when overexpressed presynaptically in the Xenopus neuromuscular junction. These observations establish Munc13-1 as a novel presynaptic target of the diacylglycerol second messenger pathway that acts in parallel with protein kinase C to regulate neurotransmitter secretion.