Mechanism and function of drosophila capa GPCR: a desiccation stress-responsive receptor with functional homology to human neuromedinU receptor

Terhzaz, S. , Cabrero, P. , Robben, J.H., Radford, J.C., Hudson, B.D. , Milligan, G. , Dow, J.A.T. and Davies, S.A. (2012) Mechanism and function of drosophila capa GPCR: a desiccation stress-responsive receptor with functional homology to human neuromedinU receptor. PLoS ONE, 7(1), e29897. (doi: 10.1371/journal.pone.0029897) (PMID:22253819) (PMCID:PMC3256212)

Abstract

The capa peptide receptor, capaR (CG14575), is a G-protein coupled receptor (GPCR) for the D. melanogaster capa neuropeptides, Drm-capa-1 and -2 (capa-1 and -2). To date, the capa peptide family constitutes the only known nitridergic peptides in insects, so the mechanisms and physiological function of ligand-receptor signalling of this peptide family are of interest. Capa peptide induces calcium signaling via capaR with EC50 values for capa-1 = 3.06 nM and capa-2 = 4.32 nM. capaR undergoes rapid desensitization, with internalization via a b-arrestin-2 mediated mechanism but is rapidly re-sensitized in the absence of capa-1. Drosophila capa peptides have a C-terminal -FPRXamide motif and insect-PRXamide peptides are evolutionarily related to vertebrate peptide neuromedinU (NMU). Potential agonist effects of human NMU-25 and the insect -PRLamides [Drosophila pyrokinins Drm-PK-1 (capa-3), Drm-PK-2 and hugin-gamma [hugg]] against capaR were investigated. NMU-25, but not hugg nor Drm-PK-2, increases intracellular calcium ([Ca2+]i) levels via capaR. In vivo, NMU-25 increases [Ca2+]i and fluid transport by the Drosophila Malpighian (renal) tubule. Ectopic expression of human NMU receptor 2 in tubules of transgenic flies results in increased [Ca2+]i and fluid transport. Finally, anti-porcine NMU-8 staining of larval CNS shows that the most highly immunoreactive cells are capa-producing neurons. These structural and functional data suggest that vertebrate NMU is a putative functional homolog of Drm-capa-1 and -2. capaR is almost exclusively expressed in tubule principal cells; cell-specific targeted capaR RNAi significantly reduces capa-1 stimulated [Ca2+]i and fluid transport. Adult capaR RNAi transgenic flies also display resistance to desiccation. Thus, capaR acts in the key fluid-transporting tissue to regulate responses to desiccation stress in the fly.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Cabrero, Mr Pablo and Dow, Professor Julian and Hudson, Dr Brian and Robben, Dr Joris and Milligan, Professor Graeme and Terhzaz, Dr Selim and Davies, Professor Shireen
• Authors: Terhzaz, S., Cabrero, P., Robben, J.H., Radford, J.C., Hudson, B.D., Milligan, G., Dow, J.A.T., and Davies, S.A.
• College/School: College of Medical Veterinary and Life Sciences > School of Molecular Biosciences; College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: PLoS ONE
• Publisher: Public Library of Science
• ISSN: 1932-6203
• ISSN (Online): 1932-6203
• Published Online: 11 January 2012
• Copyright Holders: Copyright © 2012 The Authors
• First Published: First published in PLoS ONE 2012 7(1): e29897
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
50371	1	Epithelial stress sensors: novel roles for cytochrome P450s and organellar calcium in integrated stress and immune responses.	Shireen Davies	Biotechnology and Biological Sciences Research Council (BBSRC)	BB/G020620/1	Institute of Molecular Cell and Systems Biology