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
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Research Support, N.I.H., Extramural
MeSH terms
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Acetylcholine / metabolism
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Animals
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Caenorhabditis elegans / growth & development
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Caenorhabditis elegans / metabolism*
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Caenorhabditis elegans Proteins / chemistry
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Caenorhabditis elegans Proteins / metabolism*
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Carrier Proteins
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Cholinergic Agents / metabolism
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GTP-Binding Protein alpha Subunits, G12-G13 / chemistry
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GTP-Binding Protein alpha Subunits, G12-G13 / metabolism*
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Guanine Nucleotide Exchange Factors / chemistry
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Guanine Nucleotide Exchange Factors / metabolism*
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Models, Biological
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Motor Neurons / cytology
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Motor Neurons / pathology
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Mutant Proteins / metabolism
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Neurotransmitter Agents / metabolism*
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Pharynx / abnormalities
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Presynaptic Terminals
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Promoter Regions, Genetic / genetics
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RGS Proteins / metabolism*
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Rho Guanine Nucleotide Exchange Factors
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Signal Transduction*
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rhoA GTP-Binding Protein / metabolism*
Substances
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Caenorhabditis elegans Proteins
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Carrier Proteins
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Cholinergic Agents
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GPA-12 protein, C elegans
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Guanine Nucleotide Exchange Factors
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Mutant Proteins
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Neurotransmitter Agents
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RGS Proteins
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RHGF-1 protein, C elegans
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Rho Guanine Nucleotide Exchange Factors
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phorbol ester binding protein
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GTP-Binding Protein alpha Subunits, G12-G13
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rhoA GTP-Binding Protein
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Acetylcholine