The melanin-concentrating hormone receptors: neuronal and non-neuronal functions

Abstract

Melanin-concentrating hormone (MCH) is a cyclic peptide highly conserved in vertebrates and was originally identified as a skin-paling factor in Teleosts. In fishes, MCH also participates in the regulation of the stress-response and feeding behaviour. Mammalian MCH is a hypothalamic neuropeptide that displays multiple functions, mostly controlling feeding behaviour and energy homeostasis. Transgenic mouse models and pharmacological studies have shown the importance of the MCH system as a potential target in the treatment of appetite disorders and obesity as well as anxiety and psychiatric diseases. Two G-protein-coupled receptors (GPCRs) binding MCH have been characterized so far. The first, named MCH-R1 and also called SLC1, was identified through reverse pharmacology strategies by several groups as a cognate receptor of MCH. This receptor is expressed at high levels in many brain areas of rodents and primates and is also expressed in peripheral organs, albeit at a lower rate. A second receptor, designated MCH-R2, exhibited 38% identity to MCH-R1 and was identified by sequence analysis of the human genome. Interestingly, although MCH-R2 orthologues were also found in fishes, dogs, ferrets and non-human primates, this MCH receptor gene appeared either lacking or non-functional in rodents and lagomorphs. Both receptors are class I GPCRs, whose main roles are to mediate the actions of peptides and neurotransmitters in the central nervous system. However, examples of action of MCH on neuronal and non-neuronal cells are emerging that illustrate novel MCH functions. In particular, the functionality of endogenously expressed MCH-R1 has been explored in human neuroblastoma cells, SK-N-SH and SH-SY5Y cells, and in non-neuronal cell types such as the ependymocytes. Indeed, we have identified mitogen-activated protein kinase (MAPK)-dependent or calcium-dependent signalling cascades that ultimately contributed to neurite outgrowth in neuroblastoma cells or to modulation of ciliary beating in ependymal cells. The putative role of MCH on cellular shaping and plasticity on one side and volume transmission on the other must be now considered.

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Acknowledgements

This article is dedicated in memory of Professor Wylie Vale, a pioneer in the MCH field and a major contributor in Neuroendocrinology, who passed away in January 2012. We thank Dr Erwan Bezard (IMN, CNRS UMR5293, Bordeaux, France) for his critical reading of and helpful comments on this manuscript. The work carried out in Nahon's laboratory at the IPMC was supported by the Centre National de la Recherche Scientifique (CNRS), the French National Research Agency (ANR-08-MNPS-018-01; LABEX SIGNALIFE, ANR-11-LBX-0028-01), 6th FP EU STREPS/NEST, (APES project no. 28594), the Association pour la Recherche sur le Cancer (ARC), the Fondation de France (Comité Parkinson), the ‘Association France Parkinson’, the ‘Société Française de Nutrition’, the Fondation pour la Recherche Médicale (FRM) and the <<Convention de Collaboration>> IUCPQ-Université Laval (Québec)/CNRS. We thank Professor Jeffrey M Friedman (Rockefeller University, New York, NY, USA) for kindly providing the Pmch-CFP mice and Dr A Viale (Memorial Sloan-Kettering Cancer Center, New York, NY, USA) for having performed microarray experiments and data analysis. Gregory Conductier was supported by a postdoctoral fellowship from ANR-08-MNPS-018-01, the CNRS (INSB), the Société Française de Nutrition (prize winner 2010) and the Danone Institute (prize winner 2012).

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Correspondence to J-L Nahon.

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This article is published as part of a supplement sponsored by the Université Laval's Research Chair in Obesity in an effort to inform the public on the causes, consequences, treatments and prevention of obesity.

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Presse, F., Conductier, G., Rovere, C. et al. The melanin-concentrating hormone receptors: neuronal and non-neuronal functions. Int J Obes Supp 4, S31–S36 (2014). https://doi.org/10.1038/ijosup.2014.9

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Keywords

  • AROM gene; energy balance; feeding behaviour; melanin-concentrating hormone; MCH receptors; primate-specific PMCHL genes

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