The Galpha12-RGS RhoGEF-RhoA signalling pathway regulates neurotransmitter release in C. elegans

EMBO J. 2006 Dec 13;25(24):5884-95. doi: 10.1038/sj.emboj.7601458. Epub 2006 Nov 30.

Abstract

In Caenorhabditis elegans adults, the single Rho GTPase orthologue, RHO-1, stimulates neurotransmitter release at synapses. We show that one of the pathways acting upstream of RHO-1 in acetylcholine (ACh)-releasing motor neurons depends on Galpha12 (GPA-12), which acts via the single C. elegans RGS RhoGEF (RHGF-1). Activated GPA-12 has the same effect as activated RHO-1, inducing the accumulation of diacylglycerol and the neuromodulator UNC-13 at release sites, and increased ACh release. We showed previously that RHO-1 stimulates ACh release by two separate pathways-one that requires UNC-13 and a second that does not. We show here that a non-DAG-binding-UNC-13 mutant that partially blocks increased ACh release by activated RHO-1 completely blocks increased ACh release by activated GPA-12. Thus, the upstream GPA-12/RHGF-1 pathway stimulates only a subset of RHO-1 downstream effectors, suggesting that either the RHO-1 effectors require different levels of activated RHO-1 for activation or there are two distinct pools of RHO-1 within C. elegans neurons.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetylcholine / metabolism
  • Animals
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / chemistry
  • Caenorhabditis elegans Proteins / metabolism*
  • Carrier Proteins
  • Cholinergic Agents / metabolism
  • GTP-Binding Protein alpha Subunits, G12-G13 / chemistry
  • GTP-Binding Protein alpha Subunits, G12-G13 / metabolism*
  • Guanine Nucleotide Exchange Factors / chemistry
  • Guanine Nucleotide Exchange Factors / metabolism*
  • Models, Biological
  • Motor Neurons / cytology
  • Motor Neurons / pathology
  • Mutant Proteins / metabolism
  • Neurotransmitter Agents / metabolism*
  • Pharynx / abnormalities
  • Presynaptic Terminals
  • Promoter Regions, Genetic / genetics
  • RGS Proteins / metabolism*
  • Rho Guanine Nucleotide Exchange Factors
  • Signal Transduction*
  • rhoA GTP-Binding Protein / metabolism*

Substances

  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • Cholinergic Agents
  • GPA-12 protein, C elegans
  • Guanine Nucleotide Exchange Factors
  • Mutant Proteins
  • Neurotransmitter Agents
  • RGS Proteins
  • RHGF-1 protein, C elegans
  • Rho Guanine Nucleotide Exchange Factors
  • phorbol ester binding protein
  • GTP-Binding Protein alpha Subunits, G12-G13
  • rhoA GTP-Binding Protein
  • Acetylcholine