Serotonin Inhibition of Synaptic Transmission: Galpha(0) Decreases the Abundance of UNC-13 at Release Sites

Neuron. 1999 Sep;24(1):231-42. doi: 10.1016/s0896-6273(00)80835-1.

Abstract

We show that serotonin inhibits synaptic transmission at C. elegans neuromuscular junctions, and we describe a signaling pathway that mediates this effect. Release of acetylcholine from motor neurons was assayed by measuring the sensitivity of intact animals to the acetylcholinesterase inhibitor aldicarb. By this assay, exogenous serotonin inhibited acetylcholine release, whereas serotonin antagonists stimulated release. The effects of serotonin on synaptic transmission were mediated by GOA-1 (a Galpha0 subunit) and DGK-1 (a diacylglycerol [DAG] kinase), both of which act in the ventral cord motor neurons. Mutants lacking goa-1 G(alpha)0 accumulated abnormally high levels of the DAG-binding protein UNC-13 at motor neuron nerve terminals, suggesting that serotonin inhibits synaptic transmission by decreasing the abundance of UNC-13 at release sites.

Publication types

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

MeSH terms

  • Acetylcholine / metabolism
  • Aldicarb / pharmacology
  • Amino Acid Sequence
  • Animals
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins*
  • Carrier Proteins
  • Cell Line
  • Cholinesterase Inhibitors / pharmacology
  • Diacylglycerol Kinase / chemistry
  • Diacylglycerol Kinase / genetics
  • Diacylglycerol Kinase / metabolism
  • GTP-Binding Protein alpha Subunits, Gi-Go
  • Helminth Proteins / metabolism*
  • Heterotrimeric GTP-Binding Proteins / chemistry
  • Heterotrimeric GTP-Binding Proteins / genetics
  • Heterotrimeric GTP-Binding Proteins / physiology*
  • Molecular Sequence Data
  • Motor Neurons / drug effects
  • Motor Neurons / metabolism
  • Mutation
  • Serotonin / pharmacology*
  • Signal Transduction
  • Synaptic Transmission / drug effects*

Substances

  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • Cholinesterase Inhibitors
  • Helminth Proteins
  • phorbol ester binding protein
  • Serotonin
  • Aldicarb
  • Diacylglycerol Kinase
  • GTP-Binding Protein alpha Subunits, Gi-Go
  • Heterotrimeric GTP-Binding Proteins
  • Acetylcholine