Evolutionary conservation of the structural, pharmacological, and genomic characteristics of the melanocortin receptor subtypes

Schiöth, Helgi B.; Haitina, Tatjana; Ling, Maria K.; Ringholm, Aneta; Fredriksson, Robert; Cerdá‐Reverter, José Miguel; Kloviņš, Jānis

doi:10.1016/j.peptides.2004.11.034

Cited by 124 publications

(93 citation statements)

References 107 publications

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“…In addition, initially as a result of the 2R event, four paralogous mcr genes were postulated, followed by a local gene duplication event to account for the fifth mcr gene ( Fig. 1; Schiöth et al 2003Schiöth et al , 2005.…”

Section: T121 Thematic Reviewmentioning

confidence: 99%

60 YEARS OF POMC: Melanocortin receptors: evolution of ligand selectivity for melanocortin peptides

Dores

Liang

Davis

et al. 2016

Journal of Molecular Endocrinology

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The evolution of the melanocortin receptors (MCRs) is linked to the evolution of adrenocorticotrophic hormone (ACTH), the melanocyte-stimulating hormones (MSHs), and their common precursor pro-opiomelanocortin (POMC). The origin of the MCRs and POMC appears to be grounded in the early radiation of the ancestral protochordates. During the genome duplications that have occurred during the evolution of the chordates, the organization plan for POMC was established, and features that have been retained include, the high conservation of the amino acid sequences of α-MSH and ACTH, and the presence of the HFRW MCR activation motif in all of the melanocortin peptides (i.e. ACTH, α-MSH, β-MSH, γ-MSH, and δ-MSH). For the MCRs, the chordate genome duplication events resulted in the proliferation of paralogous receptor genes, and a divergence in ligand selectivity. While most gnathostome MCRs can be activated by either ACTH or the MSHs, teleost and tetrapod MC2R orthologs can only be activated by ACTH. The appearance of the accessory protein, MRAP1, paralleled the emergence of teleost and tetrapods MC2R ligand selectivity, and the dependence of these orthologs on MRAP1 for trafficking to the plasma membrane. The accessory protein, MRAP2, does not affect MC2R ligand selectivity, but does influence the functionality of MC4R orthologs. In this regard, the roles that these accessory proteins may play in the physiology of the five MCRs (i.e. MC1R, MC2R, MC3R, MC4R, and MC5R) are discussed.

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Section: T121 Thematic Reviewmentioning

confidence: 99%

60 YEARS OF POMC: Melanocortin receptors: evolution of ligand selectivity for melanocortin peptides

Dores

Liang

Davis

et al. 2016

Journal of Molecular Endocrinology

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“…When compared with other GPCRs, the MCRs are the smallest in terms of primary sequence, with relatively short N-and C-terminal domains (Horn et al 2003). The reduction in the size of the N-terminal domain is most pronounced for teleost and tetrapod MC2R orthologs (Mountjoy et al 1992, Schiöth et al 2005.…”

Section: Overview Of Mcrs and Ligandsmentioning

confidence: 99%

MOLECULAR EVOLUTION OF GPCRS: Melanocortin/melanocortin receptors

Dores¹,

Londraville²,

Prokop³

et al. 2014

Journal of Molecular Endocrinology

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The melanocortin receptors (MCRs) are a family of G protein-coupled receptors that are activated by melanocortin ligands derived from the proprotein, proopiomelanocortin (POMC). During the radiation of the gnathostomes, the five receptors have become functionally segregated (i.e. melanocortin 1 receptor (MC1R), pigmentation regulation; MC2R, glucocorticoid synthesis; MC3R and MC4R, energy homeostasis; and MC5R, exocrine gland physiology). A focus of this review is the role that ligand selectivity plays in the hypothalamus/pituitary/adrenal-interrenal (HPA-I) axis of teleosts and tetrapods as a result of the exclusive ligand selectivity of MC2R for the ligand ACTH. A second focal point of this review is the roles that the accessory proteins melanocortin 2 receptor accessory protein 1 (MRAP1) and MRAP2 are playing in, respectively, the HPA-I axis (MC2R) and the regulation of energy homeostasis by neurons in the hypothalamus (MC4R) of teleosts and tetrapods. In addition, observations are presented on trends in the ligand selectivity parameters of cartilaginous fish, teleost, and tetrapod MC1R, MC3R, MC4R, and MC5R paralogs, and the modeling of the HFRW motif of ACTH(1-24) when compared with a-MSH. The radiation of the MCRs during the evolution of the gnathostomes provides examples of how the physiology of endocrine and neuronal circuits can be shaped by ligand selectivity, the intersession of reverse agonists (agouti-related peptides (AGRPs)), and interactions with accessory proteins (MRAPs).

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“…They have neuroendocrine and paracrine functions through binding to five tissue-specific melanocortin receptors MC 1-5 , which are well conserved among vertebrates (Schioth et al, 2005). The various melanocortins have different affinities for the five receptors with the exception of MC 2 receptor for which ACTH is the only ligand.…”

Section: Pleiotropy In the Melanocortin Systemmentioning

confidence: 99%

Association between melanism, physiology and behaviour: A role for the melanocortin system

Roulin

Ducrest

2011

European Journal of Pharmacology

125

137

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The melanocortin system is implicated in the expression of many phenotypic traits. Activation of the melanocortin MC 1 receptor by melanocortin hormones induces the production of brown/black eumelanic pigments, while activation of the four other melanocortin receptors affects other physiological and behavioural functions including stress response, energy homeostasis, anti-inflammatory and sexual activity, aggressiveness and resistance to oxidative stress. We recently proposed the hypothesis that some melanocortin-physiological and -behavioural traits are correlated within individuals. This hypothesis predicts that the degree of eumelanin production may, in some cases, be associated with the regulation of glucocorticoids, immunity, resistance to oxidative stress, energy homeostasis, sexual activity, and aggressiveness. A review of the zoological literature and detailed experimental studies in a free-living population of barn owls (Tyto alba) showed that indeed melanic coloration is often correlated with the predicted physiological and behavioural traits. Support for predictions of the hypothesis that covariations between coloration and other phenotypic traits stem from pleiotropic effects of the melanocortin system raises a number of theoretical and empirical issues from evolutionary and pharmacological point of views.

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Evolutionary conservation of the structural, pharmacological, and genomic characteristics of the melanocortin receptor subtypes

Cited by 124 publications

References 107 publications

60 YEARS OF POMC: Melanocortin receptors: evolution of ligand selectivity for melanocortin peptides

60 YEARS OF POMC: Melanocortin receptors: evolution of ligand selectivity for melanocortin peptides

MOLECULAR EVOLUTION OF GPCRS: Melanocortin/melanocortin receptors

Association between melanism, physiology and behaviour: A role for the melanocortin system

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