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  • The EMBO Journal (2006) 25, 5884 - 5895
  • doi:10.1038/sj.emboj.7601458

Published online: 30 November 2006

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

Emma Hiley1,2, Rachel McMullan1,2 and Stephen J Nurrish1,2

  1. MRC Cell Biology Unit, MRC Laboratory for Molecular Cell Biology University College, London, UK
  2. Department of Pharmacology, University College, London, UK

Correspondence to:

Stephen J Nurrish, MRC Cell Biology Unit, MRC Laboratory for Molecular Cell Biology, University College, Gower Street, London WC1E 6BT, UK. Tel.: +44 207 679 7267; Fax: +44 207 679 7805; E-mail: s.nurrish@ucl.ac.uk

Received 2 June 2006; Accepted 24 October 2006

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.

  • Keywords:

    • C. elegans,
    • G protein,
    • mUNC13,
    • neurotransmitter,
    • Rho GTPase