Facilitation of Synaptic Transmission by EGL-30 Gqalpha and EGL-8 PLCbeta: DAG Binding to UNC-13 Is Required to Stimulate Acetylcholine Release

Neuron. 1999 Oct;24(2):335-46. doi: 10.1016/s0896-6273(00)80848-x.

Abstract

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.

Publication types

  • Comment
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylcholine / metabolism
  • Amino Acid Sequence / genetics
  • Animals
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins*
  • Carrier Proteins
  • Diglycerides / metabolism
  • GTP-Binding Proteins / physiology*
  • Helminth Proteins / metabolism
  • Isoenzymes / physiology*
  • Molecular Sequence Data
  • Motor Neurons / physiology
  • Muscarinic Agonists / pharmacology
  • Neuromuscular Junction / metabolism
  • Phospholipase C beta
  • Synaptic Transmission / physiology*
  • Tetradecanoylphorbol Acetate / pharmacology
  • Tissue Distribution / physiology
  • Type C Phospholipases / physiology*

Substances

  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • Diglycerides
  • Helminth Proteins
  • Isoenzymes
  • Muscarinic Agonists
  • phorbol ester binding protein
  • Type C Phospholipases
  • Phospholipase C beta
  • GTP-Binding Proteins
  • Acetylcholine
  • Tetradecanoylphorbol Acetate