The Gα12-RGS RhoGEF-RhoA signalling pathway regulates neurotransmitter release in C. elegans

Hiley, Emma; Mcmullan, Rachel and Nurrish, Stephen J. (2006). The Gα12-RGS RhoGEF-RhoA signalling pathway regulates neurotransmitter release in C. elegans. EMBO journal, 25(24) pp. 5884–5895.

DOI: https://doi.org/10.1038/sj.emboj.7601458

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 Gα12 (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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