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Publication Detail
The Galpha12-RGS RhoGEF-RhoA signalling pathway regulates neurotransmitter release in C. elegans.
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Journal Article
  • Authors:
    Hiley E, McMullan R, Nurrish SJ
  • Publication date:
    13/12/2006
  • Pagination:
    5884, 5895
  • Journal:
    EMBO J
  • Volume:
    25
  • Issue:
    24
  • Country:
    England
  • Print ISSN:
    0261-4189
  • PII:
    7601458
  • Language:
    eng
  • Keywords:
    Acetylcholine, Animals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Carrier Proteins, Cholinergic Agents, GTP-Binding Protein alpha Subunits, G12-G13, Guanine Nucleotide Exchange Factors, Models, Biological, Motor Neurons, Mutant Proteins, Neurotransmitter Agents, Pharynx, Presynaptic Terminals, Promoter Regions, Genetic, RGS Proteins, Rho Guanine Nucleotide Exchange Factors, Signal Transduction, rhoA GTP-Binding Protein
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.
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