Format

Send to

Choose Destination
J Mol Endocrinol. 2014 Jun;52(3):T29-42. doi: 10.1530/JME-14-0050.

Molecular evolution of GPCRs: Melanocortin/melanocortin receptors.

Author information

1
Department of Biological SciencesUniversity of Denver, Denver, Colorado 80210, USADepartment of BiologyUniversity of Akron, Akron, Ohio 44325, USA rdores@du.edu.
2
Department of Biological SciencesUniversity of Denver, Denver, Colorado 80210, USADepartment of BiologyUniversity of Akron, Akron, Ohio 44325, USA.

Abstract

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 α-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).

KEYWORDS:

ACTH; MC2R; MC4R; MRAP1; MRAP2; melanocortin peptides; melanocortin receptors; α-MSH

PMID:
24868105
DOI:
10.1530/JME-14-0050
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Sheridan PubFactory
Loading ...
Support Center