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 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.
Betz
A
A
Max-Planck-Institut für Experimentelle Medizin, Abt. Molekulare Neurobiologie, Göttingen, Bundesrepublik Deutschland.
Ashery
U
U
Rickmann
M
M
Augustin
I
I
Neher
E
E
Südhof
T C
TC
Rettig
J
J
Brose
N
N
D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D002460:Cell Line; D005260:Female; D006801:Humans; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D009469:Neuromuscular Junction / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010703:Phorbol Esters / Q000378:metabolism* / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology; D014018:Tissue Distribution; D014981:Xenopus / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D010703:Phorbol Esters; D011955:Receptors, Drug; C485548:UNC13B protein, human; C103912:Unc13a protein, rat; C083141:phorbol ester binding protein; C027776:phorbol ester receptor; D011493:Protein Kinase C