MUNC13-1 IS A PRESYNAPTIC PHORBOL ESTER RECEPTOR THAT ENHANCES NEUROTRANSMITTER RELEASE

Munc13-1, a mammalian homolog of C. elegans unc-13p, is thought to be involved in the regulation of synaptic transmission. We now demonstrat e that Munc13-1 is a presynaptic high-affinity phorbol ester and diacy lglycerol 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 o f transmitter release when overexpressed presynaptically in the Xenopu s neuromuscular junction. These observations establish Munc13-1 as a n ovel presynaptic target of the diacylglycerol second messenger pathway that acts in parallel with protein kinase C to regulate neurotransmit ter secretion.