MC2R Membrane Protein Introduction

Introduction of MC2R

MC2R, encoded by MC2R gene, belongs to a seven-pass transmembrane G-protein coupled receptor family. It is one of five melanocortin receptors named MC1R–MC5R which are expressed in diverse tissues and exert multiple physiological functions including normal pigmentation, steroid production, energy homeostasis, feeding behavior and exocrine function. MC2R primarily presents in the adrenal gland and is involved in the regulation of steroidogenesis.

Function of MC2R Membrane Protein

MC2R is a specific receptor for adrenocorticotropic hormone (ACTH). The activated MC2R by ACTH can stimulate the activation of G proteins that promote the activities of adenylate cyclase, resulting in a subsequent increase in the concentration of cyclic AMP (cAMP) and regulating diverse cellular signal responses. MC2R most exists in the adrenal glands located on the top of each kidney. Studies have shown that MC2R may regulate the development of the adrenal glands before birth and the mutations in MC2R are detected in patients with salt-losing adrenal hypoplasia. Moreover, ACTH interacts with the receptor and regulate the production of steroidogenic enzymes. The enzymes can catalyze the production of steroids including cortisol and corticosterone. These hormones play essential roles in the immune system functions, maintaining normal blood sugar concentrations, and inducing nerve cell signaling in the brain. Mutations in MC2R display glucocorticoid synthesis dysfunctions in the adrenal gland, resulting in the potentially lethal condition of familial glucocorticoid deficiency (FGD). Besides, MC2R is also observed in human subcutaneous fat. In mouse adipose tissue, MC2R is associated with the release of non-esterified fatty acids from adipocytes. And the binding of MC2R and ACTH can mediate the stress response of skin and is involved in the pathophysiology of alopecia areata.

Fig.1 Schematic diagram illustrating MRAP and MRAP2 action on MC2R and MC4R, respectively and physiological consequence of MRAP and MRAP2 deficiency on adrenal steroidogenesis and energy homeostasis. (Stoddard, 2015)

Application of MC2R Membrane Protein in Literature

1. Novoselova T.V., et al. Pathophysiology of melanocortin receptors and their accessory proteins. Best Practice & Research Clinical Endocrinology & Metabolism. 2018, 32(2):93-106. PubMed ID: 29678289
   
   

   The review summarizes recent findings regarding melanocortin receptors (MCRs) and melanocortin receptors accessory proteins (MRAPs) physiology and the disorders associated with their dysfunction.

2. Zhang X., et al. Regulation of lipolytic response and energy balance by melanocortin 2 receptor accessory protein (MRAP) in adipocytes. Diabetes. 2018, 67(2):222-234. PubMed ID: 29217655
   
   

   The study shows that melanocortin 2 receptor accessory protein (MRAP) plays a critical role in the regulation of ACTH-induced adipose lipolysis and whole-body energy balance.

3. Benjamins J.A., et al. Melanocortin receptor subtypes are expressed on cells in the oligodendroglial lineage and signal ACTH protection. Journal of Neuroscience Research. 2018, 96(3), 427-435. PubMed ID: 28877366
   
   

   The study shows that MCRs on oligodendroglia (OL) and oligodendroglial precursor cells (OPC) are functional and activate signaling pathways that protect against mechanisms involved in OL damage in multiple sclerosis, suggesting potential beneficial effects in neurologic diseases.

4. Pilling L.C., et al. Human longevity: 25 genetic loci associated in 389,166 UK biobank participants. Aging. 2017, 9(12):2504-2520. PubMed ID: 29227965
   
   

   The study shows that human longevity is controlled by multiple genes in which MC2R intronic variants are associated with human longevity.

5. Fridmanis D., et al. ACTH Receptor (MC2R) Specificity: What Do We Know About Underlying Molecular Mechanisms. Frontiers in Endocrinology. 2017, 8:13. PubMed ID: 28220105
   
   

   The review summarizes the research advances of the molecular mechanisms underlying the action of adrenocorticotropic hormone receptor.

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Reference

1. Jackson D S, et al. (2015). Melanocortin receptor accessory proteins in adrenal disease and obesity. Frontiers in Neuroscience. 9, 213.

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