title: Melanocortin receptor accessory proteins in adrenal gland physiology and beyond.
abstract: The melanocortin receptor (MCR) family consists of five G-protein-coupled receptors (MC1R-MC5R) with diverse physiological roles. MC1R controls pigmentation, MC2R is a critical component of the hypothalamic-pituitary-adrenal axis, MC3R and MC4R have a vital role in energy homeostasis and MC5R is involved in exocrine function. The melanocortin receptor accessory protein (MRAP) and its paralogue MRAP2 are small single-pass transmembrane proteins that have been shown to regulate MCR expression and function. In the adrenal gland, MRAP is an essential accessory factor for the functional expression of the MC2R/ACTH receptor. The importance of MRAP in adrenal gland physiology is demonstrated by the clinical condition familial glucocorticoid deficiency, where inactivating MRAP mutations account for ∼20% of cases. MRAP is highly expressed in both the zona fasciculata and the undifferentiated zone. Expression in the undifferentiated zone suggests that MRAP could also be important in adrenal cell differentiation and/or maintenance. In contrast, the role of adrenal MRAP2, which is highly expressed in the foetal gland, is unclear. The expression of MRAPs outside the adrenal gland is suggestive of a wider physiological purpose, beyond MC2R-mediated adrenal steroidogenesis. In vitro, MRAPs have been shown to reduce surface expression and signalling of all the other MCRs (MC1,3,4,5R). MRAP2 is predominantly expressed in the hypothalamus, a site that also expresses a high level of MC3R and MC4R. This raises the intriguing possibility of a CNS role for the MRAPs.
authors: Centre for Endocrinology, Queen Mary University of London, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Charterhouse Square, London EC1M6BQ, UK.
authors: T V
authors: TV
authors: Novoselova
authors: D
authors: D
authors: Jackson
authors: D C
authors: DC
authors: Campbell
authors: A J L
authors: AJ
authors: Clark
authors: L F
authors: LF
authors: Chan
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000311:Adrenal Glands / Q000196:embryology / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D044101:Receptors, Melanocortin / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C458099:MRAP protein, human; C551627:MRAP2 protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D044101:Receptors, Melanocortin