Functions of the third intracellular loop of the human melanocortin-3 receptor

Current Pharmaceutical Design

Volumn 19, Issue 27, 2013, Pages 4831-4838

  Wang, Zhi Qiang ^a,b   Tao, Ya Xiong ^b  

^a YANGZHOU UNIVERSITY   (China)

^b AUBURN UNIVERSITY   (United States)

Author keywords

Alanine scanning mutagenesis; Binding; Melanocortin 3 receptor; Signaling

Indexed keywords

MELANOCORTIN 3 RECEPTOR;

ARTICLE; HUMAN; HUMAN CELL; IC 50; IN VITRO STUDY; LIGAND BINDING; POINT MUTATION; PRIORITY JOURNAL; PROTEIN FUNCTION; RECEPTOR OCCUPANCY; SIGNAL TRANSDUCTION; SITE DIRECTED MUTAGENESIS; STRUCTURE ACTIVITY RELATION; TRANSIENT EXPRESSION;

AFFINITY LABELS; ALPHA-MSH; AMINO ACID SUBSTITUTION; HEK293 CELLS; HUMANS; KINETICS; LIGANDS; MUTAGENESIS, SITE-DIRECTED; MUTANT PROTEINS; PROTEIN INTERACTION DOMAINS AND MOTIFS; PROTEIN STRUCTURE, TERTIARY; RADIOLIGAND ASSAY; RECEPTOR, MELANOCORTIN, TYPE 3; RECOMBINANT PROTEINS; SIGNAL TRANSDUCTION;

EID: 84881333739     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/1381612811319270005     Document Type: Article

References (67)

1. Cone RD. Anatomy and regulation of the central melanocortin system. Nature Neurosci 2005; 8: 571-8.
2. Tao YX. Molecular mechanisms of the neural melanocortin receptor dysfunction in severe early onset obesity. Mol Cell Endocrinol 2005; 239: 1-14.
3. Huszar D, Lynch CA, Fairchild-Huntress V, et al. Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 1997; 88: 131-41.
4. Balthasar N, Dalgaard LT, Lee CE, et al. Divergence of melanocortin pathways in the control of food intake and energy expenditure. Cell 2005; 123: 493-505.
5. Farooqi IS, Keogh JM, Yeo GS, Lank EJ, Cheetham T, O'Rahilly S. Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N Engl J Med 2003; 348: 1085-95.
6. Chen AS, Marsh DJ, Trumbauer ME, et al. Inactivation of the mouse melanocortin-3 receptor results in increased fat mass and reduced lean body mass. Nature Genet 2000; 26: 97-102.
7. Butler AA, Kesterson RA, Khong K, et al. A unique metabolic syndrome causes obesity in the melanocortin-3 receptor-deficient mouse. Endocrinology 2000; 141: 3518-21.
8. Sutton GM, Perez-Tilve D, Nogueiras R, et al. The melanocortin-3 receptor is required for entrainment to meal intake. J Neurosci 2008; 28: 12946-55.
9. Sutton GM, Begriche K, Kumar KG, et al. Central nervous system melanocortin-3 receptors are required for synchronizing metabolism during entrainment to restricted feeding during the light cycle. FASEB J 2010; 24: 862-72.
10. Tao YX. Mutations in the melanocortin-3 receptor (MC3R) gene: Impact on human obesity or adiposity. Curr Opin Investig Drugs 2010; 11: 1092-6.
11. Lee YS, Poh LK, Loke KY. A novel melanocortin 3 receptor gene (MC3R) mutation associated with severe obesity. J Clin Endocrinol Metab 2002; 87: 1423-6.
12. Rached M, Buronfosse A, Begeot M, Penhoat A. Inactivation and intracellular retention of the human I183N mutated melanocortin 3 receptor associated with obesity. Biochim Biophys Acta 2004; 1689: 229-34.
13. Tao YX, Segaloff DL. Functional characterization of melanocortin-3 receptor variants identify a loss-of-function mutation involving an amino acid critical for G protein-coupled receptor activation. J Clin Endocrinol Metab 2004; 89: 3936-42.
14. Lee YS, Poh LK, Kek BL, Loke KY. The role of melanocortin 3 receptor gene in childhood obesity. Diabetes 2007; 56: 2622-30.
15. Tao YX. Functional characterization of novel melanocortin-3 receptor mutations identified from obese subjects. Biochim Biophys Acta 2007; 1772: 1167-74.
16. Mencarelli M, Walker GE, Maestrini S, et al. Sporadic mutations in melanocortin receptor 3 in morbid obese individuals. Eur J Hum Genet 2008; 16: 581-6.
17. Calton MA, Ersoy BA, Zhang S, et al. Association of functionally significant Melanocortin-4 but not Melanocortin-3 receptor mutations with severe adult obesity in a large North American case-control study. Hum Mol Genet 2009; 18: 1140-7.
18. Zegers D, Beckers S, de Freitas F, et al. Identification of three novel genetic variants in the melanocortin-3 receptor of obese children. Obesity (Silver Spring) 2011; 19: 152-9.
19. Mencarelli M, Dubern B, Alili R, et al. Rare melanocortin-3 receptor mutations with in vitro functional consequences are associated with human obesity. Hum Mol Genet 2011; 20: 392-9.
20. Versteeg DH, Van Bergen P, Adan RA, De Wildt DJ. Melanocortins and cardiovascular regulation. Eur J Pharmacol 1998; 360: 1-14.
21. Ni XP, Pearce D, Butler AA, Cone RD, Humphreys MH. Genetic disruption of β-melanocyte-stimulating hormone signaling leads to salt-sensitive hypertension in the mouse. J Clin Invest 2003; 111: 1251-8.
22. Humphreys MH. β-MSH, sodium metabolism, and salt-sensitive hypertension. Am J Physiol 2004; 286: R417-R430.
23. Humphreys MH, Ni XP, Pearce D. Cardiovascular effects of melanocortins. Eur J Pharmacol 2011; 660: 43-52.
24. Mioni C, Giuliani D, Cainazzo MM, et al. Further evidence that melanocortins prevent myocardial reperfusion injury by activating melanocortin MC3 receptors. Eur J Pharmacol 2003; 477: 227-34.
25. Getting SJ. Targeting melanocortin receptors as potential novel therapeutics. Pharmacol Ther 2006; 111: 1-15.
26. Getting SJ, Riffo-Vasquez Y, Pitchford S, et al. A role for MC3R in modulating lung inflammation. Pulm Pharmacol Ther 2008; 21: 866-73.
27. Montero-Melendez T, Patel HB, Seed M, Nielsen S, Jonassen TE, Perretti M. The melanocortin agonist AP214 exerts antiinflammatory and proresolving properties. Am J Pathol 2011; 179: 259-69.
28. Manna SK, Aggarwal BB. α-Melanocyte-stimulating hormone inhibits the nuclear transcription factor NF-βB activation induced by various inflammatory agents. J Immunol 1998; 161: 2873-80.
29. Catania A, Gatti S, Colombo G, Lipton JM. Targeting melanocortin receptors as a novel strategy to control inflammation. Pharmacol Rev 2004; 56: 1-29.
30. Wess J. G-protein-coupled receptors: molecular mechanisms involved in receptor activation and selectivity of G-protein recognition. FASEB J 1997; 11: 346-54.
31. Rosenbaum DM, Rasmussen SG, Kobilka BK. The structure and function of G-protein-coupled receptors. Nature 2009; 459: 356-63.
32. Pauwels PJ, Wurch T. Review: amino acid domains involved in constitutive activation of G-protein-coupled receptors. Mol Neurobiol 1998; 17: 109-35.
33. Chee MJ, Morl K, Lindner D, et al. The third intracellular loop stabilizes the inactive state of the neuropeptide Y1 receptor. J Biol Chem 2008; 283: 33337-46.
34. Cunningham BC, Wells JA. High-resolution epitope mapping of hGH-receptor interactions by alanine-scanning mutagenesis. Science 1989; 244: 1081-5.
35. Lu ZL, Hulme EC. The functional topography of transmembrane domain 3 of the m1 muscarinic acetylcholine receptor, revealed by scanning mutagenesis. J Biol Chem 1999; 274: 7309-15.
36. Chen C, Okayama H. High-efficiency transformation of mammalian cells by plasmid DNA. Mol Cell Biol 1987; 7: 2745-52.
37. Tao YX, Segaloff DL. Functional characterization of melanocortin-4 receptor mutations associated with childhood obesity. Endocrinology 2003; 144: 4544-51.
38. Wang SX, Fan ZC, Tao YX. Functions of acidic transmembrane residues in human melanocortin-3 receptor binding and activation. Biochem Pharmacol 2008; 76: 520-30.
39. Hausdorff WP, Hnatowich M, O'Dowd BF, Caron MG, Lefkowitz RJ. A mutation of the α2-adrenergic receptor impairs agonist activation of adenylyl cyclase without affecting high affinity agonist binding. J Biol Chem 1990; 265: 1388-93.
40. Takhar S, Gyomorey S, Su RC, Mathi SK, Li X, Wheeler MB. The third cytoplasmic domain of the GLP-1[7-36 amide] receptor is required for coupling to the adenylyl cyclase system. Endocrinology 1996; 137: 2175-8.
41. Hill-Eubanks D, Burstein ES, Spalding TA, Brauner-Osborne H, Brann MR. Structure of a G-protein-coupling domain of a muscarinic receptor predicted by random saturation mutagenesis. J Biol Chem 1996; 271: 3058-65.
42. Mathi SK, Chan Y, Li X, Wheeler MB. Scanning of the glucagonlike peptide-1 receptor localizes G protein-activating determinants primarily to the N terminus of the third intracellular loop. Mol Endocrinol 1997; 11: 424-32.
43. Burstein ES, Spalding TA, Brann MR. Structure/function relationships of a G-protein coupling pocket formed by the third intracellular loop of the m5 muscarinic receptor. Biochemistry 1998; 37: 4052-8.
44. Chan KY, Pang RT, Chow BK. Functional segregation of the highly conserved basic motifs within the third endoloop of the human secretin receptor. Endocrinology 2001; 142: 3926-34.
45. Couvineau A, Lacapere JJ, Tan YV, Rouyer-Fessard C, Nicole P, Laburthe M. Identification of cytoplasmic domains of hVPAC1 receptor required for activation of adenylyl cyclase. Crucial role of two charged amino acids strictly conserved in class II G proteincoupled receptors. J Biol Chem 2003; 278: 24759-66.
46. Conner AC, Simms J, Conner MT, Wootten DL, Wheatley M, Poyner DR. Diverse functional motifs within the three intracellular loops of the CGRP1 receptor. Biochemistry 2006; 45: 12976-85.
47. Angelova K, Fanelli F, Puett D. Contributions of intracellular loops 2 and 3 of the lutropin receptor in Gs coupling. Mol Endocrinol 2008; 22: 126-38.
48. Tao YX. Mutations in melanocortin-4 receptor and human obesity. Prog Mol Biol Transl Sci 2009; 88: 173-204.
49. Tao YX. The melanocortin-4 receptor: Physiology, pharmacology, and pathophysiology. Endocr Rev 2010; 31: 506-43.
50. Wang ZQ, Tao YX. Functional studies on twenty novel naturally occurring melanocortin-4 receptor mutations. Biochim Biophys Acta 2011; 1812: 1190-9.
51. Tao YX. Inactivating mutations of G protein-coupled receptors and diseases: Structure-function insights and therapeutic implications. Pharmacol Ther 2006; 111: 949-73.
52. Tarnow P, Rediger A, Schulz A, Gruters A, Biebermann H. Identification of the translation start site of the human melanocortin 3 receptor. Obes Facts 2012; 5: 45-51.
53. Capra V, Veltri A, Foglia C, Crimaldi L, Habib A, Parenti M, Rovati GE. Mutational analysis of the highly conserved ERY motif of the thromboxane A2 receptor: alternative role in G proteincoupled receptor signaling. Mol Pharmacol 2004; 66: 880-9.
54. Rovati GE, Capra V, Neubig RR. The highly conserved DRY motif of class A G protein-coupled receptors: beyond the ground state. Mol Pharmacol 2007; 71: 959-64.
55. Ambrosio M, Fanelli F, Brocchetti S, et al. Superactive mutants of thromboxane prostanoid receptor: functional and computational analysis of an active form alternative to constitutively active mutants. Cell Mol Life Sci 2010; 67: 2979-89.
56. Tao YX, Segaloff DL. Functional analyses of melanocortin-4 receptor mutations identified from patients with binge eating disorder and nonobese or obese subjects. J Clin Endocrinol Metab 2005; 90: 5632-8.
57. Rong R, Tao YX, Cheung BM, Xu A, Cheung GC, Lam KS. Identification and functional characterization of three novel human melanocortin-4 receptor gene variants in an obese Chinese population. Clin Endocrinol 2006; 65: 198-205.
58. Fan ZC, Tao YX. Functional characterization and pharmacological rescue of melanocortin-4 receptor mutations identified from obese patients. J Cell Mol Med 2009; 13: 3268-82.
59. Tao YX, Huang H, Wang ZQ, Yang F, Williams JN, Nikiforovich GV. Constitutive activity of neural melanocortin receptors. Methods Enzymol 2010; 484: 267-79.
60. Tiberi M, Caron MG. High agonist-independent activity is a distinguishing feature of the dopamine D1B receptor subtype. J Biol Chem 1994; 269: 27925-31.
61. Hasegawa H, Negishi M, Ichikawa A. Two isoforms of the prostaglandin E receptor EP3 subtype different in agonistindependent constitutive activity. J Biol Chem 1996; 271: 1857-60.
62. Schaffer K, McBride EW, Beinborn M, Kopin AS. Interspecies polymorphisms confer constitutive activity to the Mastomys cholecystokinin-B/gastrin receptor. J Biol Chem 1998; 273: 28779-84.
63. Tao YX, Mizrachi D, Segaloff DL. Chimeras of the rat and human FSH receptors (FSHRs) identify residues that permit or suppress transmembrane 6 mutation-induced constitutive activation of the FSHR via rearrangements of hydrophobic interactions between helices 6 and 7. Mol Endocrinol 2002; 16: 1881-92.
64. Chakir K, Xiang Y, Yang D, et al. The third intracellular loop and the carboxyl terminus of 2-adrenergic receptor confer spontaneous activity of the receptor. Mol Pharmacol 2003; 64: 1048-58.
65. Zhang M, Tao YX, Ryan GL, Feng X, Fanelli F, Segaloff DL. Intrinsic differences in the response of the human lutropin receptor versus the human follitropin receptor to activating mutations. J Biol Chem 2007; 282: 25527-39.
66. Feng X, Muller T, Mizrachi D, Fanelli F, Segaloff DL. An intracellular loop (IL2) residue confers different basal constitutive activities to the human lutropin receptor and human thyrotropin receptor through structural communication between IL2 and helix 6, via helix 3. Endocrinology 2008; 149: 1705-17.
67. Tao YX. Constitutive activation of G protein-coupled receptors and diseases: Insights into mechanism of activation and therapeutics. Pharmacol Ther 2008; 120: 129-48.