Inhibition of melanocortin-4 receptor dimerization by substitutions in intracellular loop 2

Journal of Molecular Endocrinology

Volumn 51, Issue 1, 2013, Pages 109-118

  Piechowski, C L ^a   Rediger, Anne ^a   Lagemann, Christina ^a   Mühlhaus, Jessica ^a   Müller, Anne ^a   Pratzka, Juliane ^a   Tarnow, Patrick ^a   Grüters, Annette ^a   Krude, Heiko ^a   Kleinau, Gunnar ^a   Biebermann, Heike ^a  

^a CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

Author keywords

Constitutive signaling activity; Dimer dissociation; Dimerization; G protein coupled receptor; Melanocortin 4 receptor

Indexed keywords

CANNABINOID 1 RECEPTOR; CELL SURFACE RECEPTOR; CYCLIC AMP; DIMER; HOMODIMER; MELANOCORTIN 4 RECEPTOR; MONOMER;

ANIMAL CELL; ARTICLE; CELL STRUCTURE; CHIMERA; DIMERIZATION; DISSOCIATION; ENZYME LINKED IMMUNOSORBENT ASSAY; INTRACELLULAR LOOP 2; NONHUMAN; PRIORITY JOURNAL;

CONSTITUTIVE SIGNALING ACTIVITY; DIMER DISSOCIATION; DIMERIZATION; G-PROTEIN-COUPLED RECEPTOR; MELANOCORTIN-4 RECEPTOR;

AMINO ACID SUBSTITUTION; ANIMALS; CELL MEMBRANE; MODELS, MOLECULAR; MUTATION; PROTEIN BINDING; PROTEIN MULTIMERIZATION; PROTEIN STRUCTURE, SECONDARY; RECEPTOR, MELANOCORTIN, TYPE 4; SIGNAL TRANSDUCTION;

EID: 84879973967     PISSN: 09525041     EISSN: 14796813     Source Type: Journal    
DOI: 10.1530/JME-13-0061     Document Type: Article

References (43)

1. Berthouze M, Rivail L, Lucas A, Ayoub MA, Russo O, Sicsic S, Fischmeister R, Berque-Bestel I, Jockers R & Lezoualc'h F 2007 Two transmembrane Cys residues are involved in 5-HT4 receptor dimerization. Biochemical and Biophysical Research Communications 356 642-647. (doi:10.1016/j.bbrc. 2007.03.030)
2. Biebermann H, Krude H, Elsner A, Chubanov V, Gudermann T & Gruters A 2003 Autosomal-dominant mode of inheritance of a melanocortin-4 receptor mutation in a patient with severe early-onset obesity is due to a dominant-negative effect caused by receptor dimerization. Diabetes 52 2984-2988. (doi:10.2337/diabetes.52.12.2984)
3. Biebermann H, Kuhnen P, Kleinau G & Krude H 2012 The neuroendocrine circuitry controlled by POMC, MSH, and AGRP. Handbook of Experimental Pharmacology 209 47-75. (doi:10.1007/978-3-642-24716-3_3)
4. Breit A, Buch TR, Boekhoff I, Solinski HJ, Damm E & Gudermann T 2011 Alternative G protein coupling and biased agonism: new insights into melanocortin-4 receptor signalling. Molecular and Cellular Endocrinology 331 232-240. (doi:10.1016/j.mce.2010.07.007)
5. Buch TR, Heling D, Damm E, Gudermann T & Breit A 2009 Pertussis toxin-sensitive signaling of melanocortin-4 receptors in hypothalamic GT1-7 cells defines agouti-related protein as a biased agonist. Journal of Biological Chemistry 284 26411-26420. (doi:10.1074/jbc.M109.039339)
6. Carrillo JJ, Lopez-Gimenez JF & Milligan G 2004 Multiple interactions between transmembrane helices generate the oligomeric a1b-adreno-ceptor. Molecular Pharmacology 66 1123-1137. (doi:10.1124/mol.104. 001586)
7. Cone RD 2006 Studies on the physiological functions of the melanocortin system. Endocrine Reviews 27 736-749. (doi:10.1210/er.2006-0034)
8. Damian M, Martin A, Mesnier D, Pin JP & Baneres JL 2006 Asymmetric conformational changes in a GPCR dimer controlled by G-proteins. EMBO Journal 25 5693-5702. (doi:10.1038/sj.emboj.7601449)
9. Elsner A, Tarnow P, Schaefer M, Ambrugger P, Krude H, Gruters A & Biebermann H 2006 MC4R oligomerizes independently of extracellular cysteine residues. Peptides 27 372-379. (doi:10.1016/j.peptides.2005. 02.027)
10. Farooqi IS, Yeo GS & O'Rahilly S 2003 Binge eating as a phenotype of melanocortin 4 receptor gene mutations. New England Journal of Medicine 349 606-609 author reply 606-609. (doi:10.1056/ NEJM200308073490615)
11. George SR, O'Dowd BF & Lee SP 2002 G-protein-coupled receptor oligomerization and its potential for drug discovery. Nature Reviews. Drug Discovery 1 808-820. (doi:10.1038/nrd913)
12. Grant M, Collier B & Kumar U 2004 Agonist-dependent dissociation of human somatostatin receptor 2 dimers: a role in receptor trafficking. Journal of Biological Chemistry 279 36179-36183. (doi:10.1074/jbc. M407310200)
13. Guo W, Shi L, Filizola M, Weinstein H & Javitch JA 2005 Crosstalk in G protein-coupled receptors: changes at the transmembrane homodimer interface determine activation. PNAS 102 17495-17500. (doi:10.1073/pnas.0508950102)
14. Guo W, Urizar E, Kralikova M, Mobarec JC, Shi L, Filizola M & Javitch JA 2008 Dopamine D2 receptors form higher order oligomers at physiological expression levels. EMBO Journal 27 2293-2304. (doi:10.1038/emboj.2008.153)
15. Hernanz-Falcon P, Rodriguez-Frade JM, Serrano A, Juan D, del Sol A, Soriano SF, Roncal F, Gomez L, Valencia A, Martinez AC et al. 2004 Identification of amino acid residues crucial for chemokine receptor dimerization. Nature Immunology 5 216-223. (doi:10.1038/ni1027)
16. Hinney A, Bettecken T, Tarnow P, Brumm H, Reichwald K, Lichtner P, Scherag A, Nguyen TT, Schlumberger P, Rief W et al. 2006 Prevalence, spectrum, and functional characterization of melanocortin-4 receptor gene mutations in a representative population-based sample and obese adults from Germany. Journal of Clinical Endocrinology and Metabolism 91 1761-1769. (doi:10.1210/jc.2005-2056)
17. Howlett AC, Qualy JM & Khachatrian LL 1986 Involvement of Gi in the inhibition of adenylate cyclase by cannabimimetic drugs. Molecular Pharmacology 29 307-313.
18. Huang H & Tao YX 2012 Pleiotropic functions of the transmembrane domain 6 of human melanocortin-4 receptor. Journal of Molecular Endocrinology 49 237-248. (doi:10.1530/JME-12-0161)
19. Kasai RS, Suzuki KG, Prossnitz ER, Koyama-Honda I, Nakada C, Fujiwara TK & Kusumi A 2011 Full characterization of GPCR monomer-dimer dynamic equilibrium by single molecule imaging. Journal of Cell Biology 192 463-480. (doi:10.1083/jcb.201009128)
20. Krishna R, Gumbiner B, Stevens C, Musser B, Mallick M, Suryawanshi S, Maganti L, Zhu H, Han TH, Scherer L et al. 2009 Potent and selective agonism of the melanocortin receptor 4 with MK-0493 does not induce weight loss in obese human subjects: energy intake predicts lack of weight loss efficacy. Clinical Pharmacology and Therapeutics 86 659-666. (doi:10.1038/clpt.2009.167)
21. Lambert NA 2010 GPCR dimers fall apart. Science Signaling 3 pe12. (doi:10.1126/scisignal.3115pe12)
22. Lee SP, O'Dowd BF, Rajaram RD, Nguyen T & George SR 2003 D2 dopamine receptor homodimerization is mediated by multiple sites of interaction, including an intermolecular interaction involving transmembrane domain 4. Biochemistry 42 11023-11031. (doi:10.1021/bi0345539)
23. Levoye A, Dam J, Ayoub MA, Guillaume JL, Couturier C, Delagrange P & Jockers R 2006 The orphan GPR50 receptor specifically inhibits MT1 melatonin receptor function through heterodimerization. EMBO Journal 25 3012-3023. (doi:10.1038/sj.emboj.7601193)
24. Mancia F, Assur Z, Herman AG, Siegel R & Hendrickson WA 2008 Ligand sensitivity in dimeric associations of the serotonin 5HT2c receptor. EMBO Reports 9 363-369. (doi:10.1038/embor.2008.27)
25. Mo XL, Yang R & Tao YX 2012 Functions of transmembrane domain 3 of human melanocortin-4 receptor. Journal of Molecular Endocrinology 49 221-235. (doi:10.1530/JME-12-0162)
26. Moreno JL, Muguruza C, Umali A, Mortillo S, Holloway T, Pilar-Cuellar F, Mocci G, Seto J, Callado LF, Neve RL et al. 2012 Identification of three residues essential for 5-HT2A-mGlu2 receptor heteromerization and its psychoactive behavioral function. Journal of Biological Chemistry 287 44301-44319. (doi:10.1074/jbc.M112.413161)
27. Nickolls SA & Maki RA 2006 Dimerization of the melanocortin 4 receptor: a study using bioluminescence resonance energy transfer. Peptides 27 380-387. (doi:10.1016/j.peptides.2004.12.037)
28. Nijenhuis WA, Oosterom J & Adan RA 2001 AgRP(83-132) acts as an inverse agonist on the human-melanocortin-4 receptor. Molecular Endocrinology 15 164-171. (doi:10.1210/me.15.1.164)
29. Pogozheva ID, Chai BX, Lomize AL, Fong TM, Weinberg DH, Nargund RP, Mulholland MW, Gantz I & Mosberg HI 2005 Interactions of human melanocortin 4 receptor with nonpeptide and peptide agonists. Biochemistry 44 11329-11341. (doi:10.1021/bi0501840)
30. Rasmussen SG, DeVree BT, Zou Y, Kruse AC, Chung KY, Kobilka TS, Thian FS, Chae PS, Pardon E, Calinski D et al. 2011 Crystal structure of the b2 adrenergic receptor-Gs protein complex. Nature 477 549-555. (doi:10.1038/nature10361)
31. Ravindran A, Joseph PR & Rajarathnam K 2009 Structural basis for differential binding of the interleukin-8 monomer and dimer to the CXCR1 N-domain: role of coupled interactions and dynamics. Biochemistry 48 8795-8805. (doi:10.1021/bi901194p)
32. Rediger A, Tarnow P, Bickenbach A, Schaefer M, Krude H, Gruters A & Biebermann H 2009 Heterodimerization of hypothalamic G-protein-coupled receptors involved in weight regulation. Obesity Facts 2 80-86. (doi:10.1159/000209862)
33. Rediger A, Piechowski CL, Habegger K, Gruters A, Krude H, Tschop MH, Kleinau G & Biebermann H 2012 MC4R dimerization in the paraventricular nucleus and GHSR/MC3R heterodimerization in the arcuate nucleus: is there relevance for body weight regulation. Neuroendocrinology 95 277-288. (doi:10.1159/000334903)
34. Rhee MH, Bayewitch M, Avidor-Reiss T, Levy R & Vogel Z 1998 Cannabinoid receptor activation differentially regulates the various adenylyl cyclase isozymes. Journal of Neurochemistry 71 1525-1534. (doi:10.1046/j.1471-4159.1998.71041525.x)
35. Rozenfeld R & Devi LA 2010 Receptor heteromerization and drug discovery. Trends in Pharmacological Sciences 31 124-130. (doi:10.1016/ j.tips.2009.11.008)
36. Rozenfeld R & Devi LA 2011 Exploring a role for heteromerization in GPCR signalling specificity. Biochemical Journal 433 11-18. (doi:10.1042/ BJ20100458)
37. Srinivasan S, Lubrano-Berthelier C, Govaerts C, Picard F, Santiago P, Conklin BR and Vaisse C 2004 Constitutive activity of the melanocortin-4 receptor is maintained by its N-terminal domain and plays a role in energy homeostasis in humans. Journal of Clinical Investigation 114 1158-1164. (doi:10.1172/JCI21927)
38. Staubert C, Tarnow P, Brumm H, Pitra C, Gudermann T, Gruters A, Schoneberg T, Biebermann H & Rompler H 2007 Evolutionary aspects in evaluating mutations in the melanocortin 4 receptor. Endocrinology 148 4642-4648. (doi:10.1210/en.2007-0138)
39. Tao YX 2010 The melanocortin-4 receptor: physiology, pharmacology, and pathophysiology. Endocrine Reviews 31 506-543. (doi:10.1210/er.2009-0037)
40. Tarnow P, Rediger A, Brumm H, Ambrugger P, Rettenbacher E, Widhalm K, Hinney A, Kleinau G, Schaefer M, Hebebrand J et al. 2008 A heterozygous mutation in the third transmembrane domain causes a dominant-negative effect on signalling capability of the MC4R. Obesity Facts 1 155-162. (doi:10.1159/000138251)
41. Van der Ploeg LH, Martin WJ, Howard AD, Nargund RP, Austin CP, Guan X, Drisko J, Cashen D, Sebhat I, Patchett AA et al. 2002 A role for the melanocortin 4 receptor in sexual function. PNAS 99 11381-11386. (doi:10.1073/pnas.172378699)
42. Vilardaga JP, Nikolaev VO, Lorenz K, Ferrandon S, Zhuang Z & Lohse MJ 2008 Conformational cross-talk between a2A-adrenergic and mu-opioid receptors controls cell signaling. Nature Chemical Biology 4 126-131. (doi:10.1038/nchembio.64)
43. Worth CL, Kleinau G & Krause G 2009 Comparative sequence and structural analyses of G-protein-coupled receptor crystal structures and implications for molecular models. PLoS ONE 4 e7011. (doi:10.1371/journal.pone.0007011)