MC3R Membrane Protein Introduction

Introduction of MC3R

MC3R, encoded by MC3R 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. MC3R is primarily expressed in the central nervous system and involved in the regulation of energy homeostasis.

Function of MC3R Membrane Protein

MC3R is a specific receptor for melanocyte-stimulating hormone (MSH) and adrenocorticotropic hormone (ACTH) that is expressed in tissues other than the adrenal cortex and melanocytes. The activated MC3R by ACTH and MSH can stimulate the activation of G proteins that activate adenylate cyclase, resulting in a subsequent increase in the concentration of cyclic AMP (cAMP) and regulating diverse cellular signal responses. Studies have indicated that MC3R influences energy intake and energy expenditure. It is observed that mutations in MC3R gene are associated with risk of adiposity gain during early childhood. Hence, MC3R may play an important role in the regulation of energy homeostasis and can act as a potential therapeutic target for obesity. Besides, MC3R also participates in the regulation of a circadian rhythm of activity related to feeding behavior and the anti-inflammatory processes. Studies have shown that MC3R may be involved in the progression of inflammatory diseases, such as pulmonary tuberculosis, arthritis, dental arthritis and inflammatory arthritis.

Fig.1 Dimerization between MC3R and GHSR1a results in amplification of MC3R signaling and attenuation of GHSR1a signaling. (Martin, 2015)

Application of MC3R Membrane Protein in Literature

1. Koya C., et al. Association between two common missense substitutions, Thr6Lys and Val81Ile, in MC3R gene and childhood obesity: a meta-analysis. Child Obes. 2018. 14(4):218-226. PubMed ID: 29688747
   
   

   The meta-analysis study shows that Thr6Lys and Val81Ile in MC3R gene are associated with the obesity susceptibility in childhood. But the conclusion needs more researches because of high clinical heterogeneity.

2. Ahmadi F., et al. Modulatory function of NMDA glutamate receptor on MC3/MC4, receptors agonist-induced hypophagia in neonatal meat-type chicken. Veterinary Research Communications. 2017, 41(4):241-248. PubMed ID: 28589422
   
   

   The article suggests that MC3 and MC4 receptors have an inhibitory role in food intake and this effect is probably mediated by NMDA glutamate receptors in neonatal chickens.

3. Zhang J., et al. The interaction of MC3R and MC4R with MRAP2, ACTH, α-MSH and AgRP in chickens. Journal of Endocrinology. 2017, 234(2):155-174. PubMed ID: 28512117
   
   

   The study suggests that α-MSH/ACTH, AgRP and MRAP2 may interact at the MC4R(/MC3R) interface to control energy balance. And it is proved that MRAP2 (and MRAP) is involved in fine-tuning the constitutive activity and ligand sensitivity and selectivity of both MC3R and MC4R in vertebrates.

4. Andersen M., et al. Melanocortin 2, 3 and 4 receptor gene expressions are downregulated in CD8+ T cytotoxic lymphocytes and CD19+ B lymphocytes in rheumatoid arthritis responding to TNFα inhibition. Scandinavian Journal of Immunology. 2017, 86(1):31-39. PubMed ID: 28426141
   
   

   The study shows that the expressions of MC1-5R in all lymphocyte subtypes reduce in responders and increase in the non-responder. And in responders, the MC2R, MC3R and MC4R gene expressions in CD8⁺ Tc and CD19⁺ B lymphocytes significantly decrease.

5. Yang Z., et al. Mutations in melanocortin-3 receptor gene and human obesity. Progress in Molecular Biology & Translational Science. 2016, 140:97-129. PubMed ID: 27288827
   
   

   The study summarizes the mutations in MC3R gene are involved in human obesity and proposes MC3R mutations can act as potential therapeutic strategies for obesity.

MC3R Preparation Options

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Reference

1. Martin W and Alfonso A. (2015). Growth hormone secretagogue receptor dimers: a new pharmacological target. Eneuro. 2(2),1-16.

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