title: Views on the co-evolution of the melanocortin-2 receptor, MRAPs, and the hypothalamus/pituitary/adrenal-interrenal axis.
abstract: A critical regulatory component of the hypothalamus/pituitary/adrenal axis (HPA) in mammals, reptiles and birds, and in the hypothalamus/pituitary/interrenal (HPI) axis of amphibians and teleosts (modern bony fishes) is the strict ligand selectivity of the melanocortin-2 receptor (MC2R). Tetrapod and teleost MC2R orthologs can only be activated by the anterior pituitary hormone, ACTH, but not by any of the MSH-sized ligands coded in POMC. In addition, both tetrapod and teleost MC2R orthologs require co-expression with the accessory protein, MRAP. However, the MC2R ortholog of the elephant shark, a cartilaginous fish, can be activated by either ACTH or the MSH-sized ligands, and the elephant shark MC2R ortholog does not require co-expression with an MRAP for activation. Given these observations, this review will provide a scenario for the co-evolution of MC2R and MRAP, based on the assumption that the obligate interaction between MC2R and MRAP evolved during the early radiation of the ancestral bony fishes.
authors.affiliation: Department of Biological Sciences, University of Denver, Denver, CO 80210, USA. Electronic address: rdores@du.edu.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Dores
authors.affiliation: Department of Biological Sciences, University of Denver, Denver, CO 80210, USA.
authors.forename: Yesenia
authors.initials: Y
authors.lastname: Garcia
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019143:Evolution, Molecular; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D010913:Pituitary-Adrenal System / Q000378:metabolism*; D044103:Receptor, Melanocortin, Type 2 / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; D044103:Receptor, Melanocortin, Type 2
keywords: HPA; HPI; MC2R; MC5R; MRAP; MRAP2