Facilitation of synaptic transmission by EGL-30 Gqalpha and EGL-8 PLCbeta: DAG binding to UNC-13 is required to stimulate acetylcholine release.
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.
Lackner
M R
MR
Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA.
Nurrish
S J
SJ
Kaplan
J M
JM
D000109:Acetylcholine / Q000378:metabolism; D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D004075:Diglycerides / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000502:physiology*; D015801:Helminth Proteins / Q000378:metabolism; D007527:Isoenzymes / Q000502:physiology*; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000502:physiology; D018721:Muscarinic Agonists / Q000494:pharmacology; D009469:Neuromuscular Junction / Q000378:metabolism; D054799:Phospholipase C beta; D009435:Synaptic Transmission / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014018:Tissue Distribution / Q000502:physiology; D010738:Type C Phospholipases / Q000502:physiology*
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D004075:Diglycerides; D015801:Helminth Proteins; D007527:Isoenzymes; D018721:Muscarinic Agonists; C083141:phorbol ester binding protein; D010738:Type C Phospholipases; D054799:Phospholipase C beta; D019204:GTP-Binding Proteins; D000109:Acetylcholine; D013755:Tetradecanoylphorbol Acetate