We show that neurotransmitter release at Caenorhabditis elegans neuromuscular junctions is facilitated by a presynaptic pathway composed of a Gqalpha (EGL-30), EGL-8 phospholipase Cbeta (PLCbeta), and the diacylglycerol- (DAG-) binding protein UNC-13. Activation of this pathway increased release of acetylcholine at neuromuscular junctions, whereas inactivation decreased release. Phorbol esters stimulated acetylcholine release, and this effect was blocked by a mutation that eliminates phorbol ester binding to UNC-13. Expression of a constitutively membrane-bound form of UNC-13 restored acetylcholine release to mutants lacking the
egl-8 PLCbeta. Activation of this pathway with muscarinic agonists caused UNC-13 to accumulate in punctate structures in the ventral nerve cord. These results suggest that presynaptic DAG facilitates synaptic transmission and that part of this effect is mediated by UNC-13.AD - Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA.FAU - Lackner, M RAU - Lackner MRFAU - Nurrish, S JAU - Nurrish SJFAU - Kaplan, J MAU - Kaplan JMLA - engID - GM54728/GM/NIGMSPT - Journal ArticleCY - UNITED STATESTA - NeuronJID - 8809320RN - 0 (Diglycerides)RN - 0 (Helminth Proteins)RN - 0 (Isoenzymes)RN - 0 (Muscarinic Agonists)RN - 0 (Unc-13 protein)RN - 16561-29-8 (Tetradecanoylphorbol Acetate)RN - 51-84-3 (Acetylcholine)RN - EC 3.1.4.- (phospholipase C beta)RN - EC 3.1.4.3 (Phospholipase C)RN - EC 3.6.1.- (GTP-Binding Proteins)SB - IM