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Activation of RHO-1 in cholinergic motor neurons competes with dopamine signalling to control locomotion

Essmann, CL; Ryan, KR; Elmr, M; Bryon-Dodd, K; Porter, A; Vaughan, A; McMullan, R; (2018) Activation of RHO-1 in cholinergic motor neurons competes with dopamine signalling to control locomotion. PLoS One , 13 (9) , Article e0204057. 10.1371/journal.pone.0204057. Green open access

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Abstract

The small GTPase RhoA plays a crucial role in the regulation of neuronal signalling to generate behaviour. In the developing nervous system RhoA is known to regulate the actin cytoskeleton, however the effectors of RhoA-signalling in adult neurons remain largely unidentified. We have previously shown that activation of the RhoA ortholog (RHO-1) in C. elegans cholinergic motor neurons triggers hyperactivity of these neurons and loopy locomotion with exaggerated body bends. This is achieved in part through increased diacylglycerol (DAG) levels and the recruitment of the synaptic vesicle protein UNC-13 to synaptic release sites, however other pathways remain to be identified. Dopamine, which is negatively regulated by the dopamine re-uptake transporter (DAT), has a central role in modulating locomotion in both humans and C. elegans. In this study we identify a new pathway in which RHO-1 regulates locomotory behaviour by repressing dopamine signalling, via DAT-1, linking these two pathways together. We observed an upregulation of dat-1 expression when RHO-1 is activated and show that loss of DAT-1 inhibits the loopy locomotion phenotype caused by RHO-1 activation. Reducing dopamine signalling in dat-1 mutants through mutations in genes involved in dopamine synthesis or in the dopamine receptor DOP-1 restores the ability of RHO-1 to trigger loopy locomotion in dat-1 mutants. Taken together, we show that negative regulation of dopamine signalling via DAT-1 is necessary for the neuronal RHO-1 pathway to regulate locomotion.

Type: Article
Title: Activation of RHO-1 in cholinergic motor neurons competes with dopamine signalling to control locomotion
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0204057
Publisher version: http://dx.doi.org/10.1371/journal.pone.0204057
Language: English
Additional information: © 2018 Essmann et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, CAENORHABDITIS-ELEGANS, NEUROTRANSMITTER RELEASE, C.-ELEGANS, TRANSPORTER TRAFFICKING, MONOAMINE TRANSPORTERS, SYNAPTIC LOCALIZATION, UNC-31 CAPS, GENE, PATHWAY, ENDOCYTOSIS
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Computer Science
URI: https://discovery.ucl.ac.uk/id/eprint/10058789
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