The melanocortin receptors and their accessory proteins

Frontiers in Endocrinology

Volumn 4, Issue FEB, 2013, Pages

  Ramachandrappa, Shwetha ^a   Gorrigan, Rebecca J ^a   Clark, Adrian J L ^a   Chan, Li F ^a  

^a QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

Author keywords

Accessory proteins; Adrenal cortex; Familial glucocorticoid deficiency; Melanocortin receptors; Obesity

Indexed keywords

CORTICOTROPIN; GLUCOCORTICOID; HYPOPHYSIS HORMONE; INTERMEDIN; MELANOCORTIN; MELANOCORTIN 1 RECEPTOR; MELANOCORTIN 2 RECEPTOR; MELANOCORTIN 3 RECEPTOR; MELANOCORTIN 4 RECEPTOR; MELANOCORTIN 5 RECEPTOR; MELANOCORTIN RECEPTOR; MELANOCORTIN RECEPTOR ACCESSORY PROTEIN; PROOPIOMELANOCORTIN; UNCLASSIFIED DRUG;

ADIPOCYTE; CELL MIGRATION; HUMAN; NONHUMAN; PROTEIN ANALYSIS; PROTEIN EXPRESSION; PROTEIN INTERACTION; PROTEIN STRUCTURE; REVIEW; SIGNAL TRANSDUCTION;

EID: 84878740198     PISSN: None     EISSN: 16642392     Source Type: Journal    
DOI: 10.3389/fendo.2013.00009     Document Type: Review

References (61)

1. Agulleiro, M. J., Roy, S., Sanchez, E., Puchol, S., Gallo-Payet, N., and Cerda-Reverter, J. M. (2010). Role of melanocortin receptor accessory proteins in the function of zebrafish melanocortin receptor type 2. Mol. Cell. Endocrinol. 320, 145-152.
2. Balthasar, N., Dalgaard, L. T., Lee, C. E., Yu, J., Funahashi, H., Williams, T., et al. (2005). Divergence of melanocortin pathways in the control of food intake and energy expenditure. Cell 123, 493-505.
3. Beaumont, K. A., Smit, D. J., Liu, Y. Y., Chai, E., Patel, M. P., Millhauser, G. L., et al. (2012). Melanocortin-1 receptor-mediated signalling pathways activated by NDP-MSH and HBD3 ligands. Pigment Cell Melanoma Res. 25, 370-374.
4. Breit, A., Wolff, K., Kalwa, H., Jarry, H., Buch, T., and Gudermann, T. (2006). The natural inverse agonist agouti-related protein induces arrestin-mediated endocytosis of melanocortin-3 and -4 receptors. J. Biol. Chem. 281, 37447-37456.
5. Butler, A. A., Kesterson, R. A., Khong, K., Cullen, M. J., Pelleymounter, M. A., Dekoning, J., et al. (2000). A unique metabolic syndrome causes obesity in the melanocortin-3 receptor-deficient mouse. Endocrinology 141, 3518-3521.
6. Chan, L. F., Metherell, L. A., Krude, H., Ball, C., O'Riordan, S. M., Costigan, C., et al. (2009a). Homozygous nonsense and frameshift mutations of the ACTH receptor in children with familial glucocorticoid deficiency (FGD) are not associated with long-term mineralocorticoid deficiency. Clin. Endocrinol. 71, 171-175.
7. Chan, L. F., Webb, T. R., Chung, T.-T., Meimaridou, E., Cooray, S. N., Guasti, L., et al. (2009b). MRAP and MRAP2 are bidirectional regulators of the melanocortin receptor family. Proc. Natl. Acad. Sci. U.S.A. 106, 6146-6151.
8. Chen, A. S., Marsh, D. J., Trumbauer, M. E., Frazier, E. G., Guan, X. M., Yu, H., et al. (2000). Inactivation of the mouse melanocortin-3 receptor results in increased fat mass and reduced lean body mass. Nat. Genet. 26, 97-102.
9. Chen, W., Kelly, M. A., Opitz-Araya, X., Thomas, R. E., Low, M. J., and Cone, R. D. (1997). Exocrine gland dysfunction in MC5-R-deficient mice: evidence for coordinated regulation of exocrine gland function by melanocortin peptides. Cell 91, 789-798.
10. Cheung, C. C., Clifton, D. K., and Steiner, R. A. (1997). Proopiomelanocortin neurons are direct targets for leptin in the hypothalamus. Endocrinology 138, 4489-4492.
11. Chung, T. T., Chan, L. F., Metherell, L. A., and Clark, A. J. (2010). Phenotypic characteristics of familial glucocorticoid deficiency (FGD) type 1 and 2. Clin. Endocrinol. 72, 589-594.
12. Clark, A. J., Mcloughlin, L., and Grossman, A. (1993). Familial glucocorticoid deficiency associated with point mutation in the adrenocorticotropin receptor. Lancet 341, 461-462.
13. Cone, R. D. (2006). Studies on the physiological functions of the melanocortin system. Endocr. Rev. 27, 736-749.
14. Cooray, S. N., Almiro Do Vale, I., Leung, K.-Y., Webb, T. R., Chapple, J. P., Egertova, M., et al. (2008). The melanocortin 2 receptor accessory protein exists as a homodimer and is essential for the function of the melanocortin 2 receptor in the mouse Y1 cell line. Endocrinology 149, 1935-1941.
15. Cooray, S. N., Chung, T. T., Mazhar, K., Szidonya, L., and Clark, A. J. (2011). Bioluminescence resonance energy transfer reveals the adrenocorticotropin (ACTH)-induced conformational change of the activated ACTH receptor complex in living cells. Endocrinology 152, 495-502.
16. Eipper, B. A., and Mains, R. E. (1980). Structure and biosynthesis of pro-adrenocorticotropin/endorphin and related peptides. Endocr. Rev. 1, 1-27.
17. Farooqi, I. S., Keogh, J. M., Yeo, G. S., Lank, E. J., Cheetham, T., and O'Rahilly, S. (2003). Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N. Engl. J. Med. 348, 1085-1095.
18. Gineau, L., Cognet, C., Kara, N., Lach, F. P., Dunne, J., Veturi, U., et al. (2012). Partial MCM4 deficiency in patients with growth retardation, adrenal insufficiency, and natural killer cell deficiency. J. Clin. Invest. 122, 821-832.
19. Gorrigan, R. J., Guasti, L., King, P., Clark, A. J. L., and Chan, L. F. (2011). Localisation of the melanocortin-2-receptor and its accessory proteins in the developing and adult adrenal gland. J. Mol. Endocrinol. 46, 227-232.
20. Hoch, M., Eberle, A. N., Wagner, U., Bussmann, C., Peters, T., and Peterli, R. (2007). Expression and localization of melanocortin-1 receptor in human adipose tissues of severely obese patients. Obesity (Silver Spring) 15, 40-49.
21. Hoch, M., Hirzel, E., Lindinger, P., Eberle, A. N., Linscheid, P., Martin, I., et al. (2008). Weak functional coupling of the melanocortin-1 receptor expressed in human adipocytes. J. Recept. Signal Transduct. Res. 28, 485-504.
22. Hughes, C. R., Chung, T. T., Habeb, A. M., Kelestimur, F., Clark, A. J., and Metherell, L. A. (2010). Missense mutations in the melanocortin 2 receptor accessory protein that lead to late onset familial glucocorticoid deficiency type 2. J. Clin. Endocrinol. Metab. 95, 3497-3501.
23. Hughes, C. R., Guasti, L., Meimaridou, E., Chuang, C. H., Schimenti, J. C., King, P. J., et al. (2012). MCM4 mutation causes adrenal failure, short stature, and natural killer cell deficiency in humans. J. Clin. Invest. 122, 814-820.
24. Huszar, D., Lynch, C. A., Fairchild-Huntress, V., Dunmore, J. H., Fang, Q., Berkemeier, L. R., et al. (1997). Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 88, 131-141.
25. Jun, D. J., Na, K. Y., Kim, W., Kwak, D., Kwon, E. J., Yoon, J. H., et al. (2010). Melanocortins induce interleukin 6 gene expression and secretion through melanocortin receptors 2 and 5 in 3T3-L1 adipocytes. J. Mol. Endocrinol. 44, 225-236.
26. Lin, L., Hindmarsh, P. C., Metherell, L. A., Alzyoud, M., Al-Ali, M., Brain, C. E., et al. (2007). Severe loss-of-function mutations in the adrenocorticotropin receptor (ACTHR, MC2R) can be found in patients diagnosed with salt-losing adrenal hypoplasia. Clin. Endocrinol. 66, 205-210.
27. Lu, D., Willard, D., Patel, I. R., Kadwell, S., Overton, L., Kost, T., et al. (1994). Agouti protein is an antagonist of the melanocyte-stimulating-hormone receptor. Nature 371, 799-802.
28. Meimaridou, E., Kowalczyk, J., Guasti, L., Hughes, C. R., Wagner, F., Frommolt, P., et al. (2012). Mutations in NNT encoding nicotinamide nucleotide transhydrogenase cause familial glucocorticoid deficiency. Nat. Genet. 44, 740-742.
29. Mencarelli, M., Dubern, B., Alili, R., Maestrini, S., Benajiba, L., Tagliaferri, M., et al. (2011). Rare melanocortin-3 receptor mutations with in vitro functional consequences are associated with human obesity. Hum. Mol. Genet. 20, 392-399.
30. Metherell, L. A., Chapple, J. P., Cooray, S., David, A., Becker, C., Ruschendorf, F., et al. (2005). Mutations in MRAP, encoding a new interacting partner of the ACTH receptor, cause familial glucocorticoid deficiency type 2. Nat. Genet. 37, 166-170.
31. Metherell, L. A., Naville, D., Halaby, G., Begeot, M., Huebner, A., Nurnberg, G., et al. (2009). Nonclassic lipoid congenital adrenal hyperplasia masquerading as familial glucocorticoid deficiency. J. Clin. Endocrinol. Metab. 94, 3865-3871.
32. Moller, C. L., Raun, K., Jacobsen, M. L., Pedersen, T. A., Holst, B., Conde-Frieboes, K. W., et al. (2011). Characterization of murine melanocortin receptors mediating adipocyte lipolysis and examination of signalling pathways involved. Mol. Cell. Endocrinol. 341, 9-17.
33. Morgan, C., and Cone, R. D. (2006). Melanocortin-5 receptor deficiency in mice blocks a novel pathway influencing pheromone-induced aggression. Behav. Genet. 36, 291-300.
34. Morgan, C., Thomas, R. E., and Cone, R. D. (2004). Melanocortin-5 receptor deficiency promotes defensive behavior in male mice. Horm. Behav. 45, 58-63.
35. Mountjoy, K. G., Mortrud, M. T., Low, M. J., Simerly, R. B., and Cone, R. D. (1994). Localization of the melanocortin-4 receptor (MC4-R) in neuroendocrine and autonomic control circuits in the brain. Mol. Endocrinol. 8, 1298-1308.
36. Nijenhuis, W. A., Oosterom, J., and Adan, R. A. (2001). AgRP(83-132) acts as an inverse agonist on the human-melanocortin-4 receptor. Mol. Endocrinol. 15, 164-171.
37. O'Riordan, S. M., Lynch, S. A., Hindmarsh, P. C., Chan, L. F., Clark, A. J., and Costigan, C. (2008). A novel variant of familial glucocorticoid deficiency prevalent among the Irish Traveler population. J. Clin. Endocrinol. Metab. 93, 2896-2899.
38. Patten, C. S., Daniels, D., Suzuki, A., Fluharty, S. J., and Yee, D. K. (2007). Structural and signaling requirements of the human melanocortin 4 receptor for MAP kinase activation. Regul. Pept. 142, 111-122.
39. Rodrigues, A. R., Pignatelli, D., Almeida, H., and Gouveia, A. M. (2009). Melanocortin 5 receptor activates ERK1/2 through a PI3K-regulated signaling mechanism. Mol. Cell. Endocrinol. 303, 74-81.
40. Roselli-Rehfuss, L., Mountjoy, K. G., Robbins, L. S., Mortrud, M. T., Low, M. J., Tatro, J. B., et al. (1993). Identification of a receptor for gamma melanotropin and other proopiomelanocortin peptides in the hypothalamus and limbic system. Proc. Natl. Acad. Sci. U.S.A. 90, 8856-8860.
41. Rumie, H., Metherell, L. A., Clark, A. J., Beauloye, V., and Maes, M. (2007). Clinical and biological phenotype of a patient with familial glucocorticoid deficiency type 2 caused by a mutation of melanocortin 2 receptor accessory protein. Eur. J. Endocrinol. 157, 539-542.
42. Schwartz, M. W., Seeley, R. J., Woods, S. C., Weigle, D. S., Campfield, L. A., Burn, P., et al. (1997). Leptin increases hypothalamic pro-opiomelanocortin mRNA expression in the rostral arcuate nucleus. Diabetes 46, 2119-2123.
43. Sebag, J. A., and Hinkle, P. M. (2007). Melanocortin-2 receptor accessory protein MRAP forms antiparallel homodimers. Proc. Natl. Acad. Sci. U.S.A. 104, 20244-20249.
44. Sebag, J. A., and Hinkle, P. M. (2009a). Opposite effects of the melanocortin-2 (MC2) receptor accessory protein MRAP on MC2 and MC5 receptor dimerization and trafficking. J. Biol. Chem. 284, 22641-22648.
45. Sebag, J. A., and Hinkle, P. M. (2009b). Regions of melanocortin 2 (MC2) receptor accessory protein necessary for dual topology and MC2 receptor trafficking and signaling. J. Biol. Chem. 284, 610-618.
46. Sebag, J. A., and Hinkle, P. M. (2010). Regulation of G protein-coupled receptor signaling: specific dominant-negative effects of melanocortin 2 receptor accessory protein 2. Sci. Signal. 3, ra28.
47. Seng Lee, Y., Kok Seng Poh, L., Lay Kee Kek, B., and Yin Loke, K. (2007). The role of melanocortin 3 receptor gene in childhood obesity. Diabetes 56, 2622-2630.
48. Sutton, G. M., Begriche, K., Kumar, K. G., Gimble, J. M., Perez-Tilve, D., Nogueiras, R., et al. (2010). Central nervous system melanocortin-3 receptors are required for synchronizing metabolism during entrainment to restricted feeding during the light cycle. FASEB J. 24, 862-872.
49. Sutton, G. M., Duos, B., Patterson, L. M., and Berthoud, H. R. (2005). Melanocortinergic modulation of cholecystokinin-induced suppression of feeding through extracellular signal-regulated kinase signaling in rat solitary nucleus. Endocrinology 146, 3739-3747.
50. Sutton, G. M., Perez-Tilve, D., Nogueiras, R., Fang, J., Kim, J. K., Cone, R. D., et al. (2008). The melanocortin-3 receptor is required for entrainment to meal intake. J. Neurosci. 28, 12946-12955.
51. Swope, V. B., Jameson, J. A., Mcfarland, K. L., Supp, D. M., Miller, W. E., Mcgraw, D. W., et al. (2012). Defining MC1R regulation in human melanocytes by its agonist alpha-melanocortin and antagonists agouti signaling protein and beta-defensin 3. J. Invest. Dermatol. 132, 2255-2262.
52. Tsigos, C., Arai, K., Hung, W., and Chrousos, G. P. (1993). Hereditary isolated glucocorticoid deficiency is associated with abnormalities of the adrenocorticotropin receptor gene. J. Clin. Invest. 92, 2458-2461.
53. Turan, S., Hughes, C., Atay, Z., Guran, T., Haliloglu, B., Clark, A. J., et al. (2012). An atypical case of familial glucocorticoid deficiency without pigmentation caused by coexistent homozygous mutations in MC2R (T152K) and MC1R (R160W). J. Clin. Endocrinol. Metab. 97, E771-E774.
54. Vage, D. I., Lu, D., Klungland, H., Lien, S., Adalsteinsson, S., and Cone, R. D. (1997). A non-epistatic interaction of agouti and extension in the fox, Vulpes vulpes. Nat. Genet. 15, 311-315.
55. Vaisse, C., Clement, K., Guy-Grand, B., and Froguel, P. (1998). A frameshift mutation in human MC4R is associated with a dominant form of obesity. Nat. Genet. 20, 113-114.
56. Valverde, P., Healy, E., Jackson, I., Rees, J. L., and Thody, A. J. (1995). Variants of the melanocyte-stimulating hormone receptor gene are associated with red hair and fair skin in humans. Nat. Genet. 11, 328-330.
57. Vongs, A., Lynn, N. M., and Rosenblum, C. I. (2004). Activation of MAP kinase by MC4-R through PI3 kinase. Regul. Pept. 120, 113-118.
58. Webb, T. R., Chan, L., Cooray, S. N., Cheetham, M. E., Chapple, J. P., and Clark, A. J. L. (2009). Distinct melanocortin 2 receptor accessory protein domains are required for melanocortin 2 receptor interaction and promotion of receptor trafficking. Endocrinology 150, 720-726.
59. Willer, C. J., Speliotes, E. K., Loos, R. J., Li, S., Lindgren, C. M., Heid, I. M., et al. (2009). Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat. Genet. 41, 25-34.
60. Xu, A., Choi, K. L., Wang, Y., Permana, P. A., Xu, L. Y., Bogardus, C., et al. (2002). Identification of novel putative membrane proteins selectively expressed during adipose conversion of 3T3-L1 cells. Biochem. Biophys. Res. Commun. 293, 1161-1167.
61. Yeo, G. S., Farooqi, I. S., Aminian, S., Halsall, D. J., Stanhope, R. G., and O'Rahilly, S. (1998). A frameshift mutation in MC4R associated with dominantly inherited human obesity. Nat. Genet. 20, 111-112.