The Galpha12-RGS RhoGEF-RhoA signalling pathway regulates neurotransmitter release in C. elegans.
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.
Hiley
Emma
E
MRC Cell Biology Unit, MRC Laboratory for Molecular Cell Biology, University College London, Gower Sttreet, London, UK.
McMullan
Rachel
R
Nurrish
Stephen J
SJ
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000378:metabolism*; D002352:Carrier Proteins; D018678:Cholinergic Agents / Q000378:metabolism; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000737:chemistry / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000378:metabolism*; D008954:Models, Biological; D009046:Motor Neurons / Q000166:cytology / Q000473:pathology; D050505:Mutant Proteins / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010614:Pharynx / Q000002:abnormalities; D017729:Presynaptic Terminals; D011401:Promoter Regions, Genetic / Q000235:genetics; D020710:RGS Proteins / Q000378:metabolism*; D064067:Rho Guanine Nucleotide Exchange Factors; D015398:Signal Transduction; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D018678:Cholinergic Agents; C516803:GPA-12 protein, C elegans; D020662:Guanine Nucleotide Exchange Factors; D050505:Mutant Proteins; D018377:Neurotransmitter Agents; D020710:RGS Proteins; C516804:RHGF-1 protein, C elegans; D064067:Rho Guanine Nucleotide Exchange Factors; C083141:phorbol ester binding protein; D044365:GTP-Binding Protein alpha Subunits, G12-G13; D020742:rhoA GTP-Binding Protein; D000109:Acetylcholine