The G protein-coupled receptor heterodimer network (GPCR-HetNet) and its hub components

International Journal of Molecular Sciences

Volumn 15, Issue 5, 2014, Pages 8570-8590

  Borroto Escuela, Dasiel O ^a   Brito, Ismel ^a,b   Romero Fernandez, Wilber ^a   Di Palma, Michael ^a,c   Oflijan, Julia ^d   Skieterska, Kamila ^e   Duchou, Jolien ^e   Van Craenenbroeck, Kathleen ^e   Suárez Boomgaard, Diana ^f   Rivera, Alicia ^f   Guidolin, Diego ^g   Agnati, Luigi F ^a   Fuxe, Kjell ^a  

^a KAROLINSKA INSTITUTE   (Sweden)

^b ARTIFICIAL INTELLIGENCE RESEARCH INSTITUTE IIIA CSIC   (Spain)

^c UNIVERSITY OF URBINO   (Italy)

^d UNIVERSITY OF TARTU   (Estonia)

^e GHENT UNIVERSITY   (Belgium)

^f UNIVERSITY OF MÁLAGA   (Spain)

^g UNIVERSITY OF PADOVA   (Italy)

Author keywords

Architecture; Clusters; Dimerization; G protein coupled receptors; Heterodimerization; Heteromers; Hubs; Network; Oligomerization; Receptor receptor interactions

Indexed keywords

ADENOSINE A1 RECEPTOR; ADENOSINE A2A RECEPTOR; BETA 2 ADRENERGIC RECEPTOR; DELTA OPIATE RECEPTOR; DOPAMINE 2 RECEPTOR; G PROTEIN COUPLED RECEPTOR; GHRELIN RECEPTOR; HETERODIMER; KAPPA OPIATE RECEPTOR; MU OPIATE RECEPTOR;

ARTICLE; PARAMETERS; PROTEIN EXPRESSION; RECEPTOR BINDING; SPECIFICITY; ALGORITHM; CHEMICAL STRUCTURE; CHEMISTRY; CLUSTER ANALYSIS; COMPUTER INTERFACE; DIMERIZATION; HUMAN; INTERNET; METABOLISM; PROTEIN DATABASE;

ALGORITHMS; CLUSTER ANALYSIS; DATABASES, PROTEIN; DIMERIZATION; HUMANS; INTERNET; METABOLIC NETWORKS AND PATHWAYS; MODELS, MOLECULAR; RECEPTORS, G-PROTEIN-COUPLED; USER-COMPUTER INTERFACE;

EID: 84900812584     PISSN: 16616596     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms15058570     Document Type: Article

References (87)

1. Brinda, K.V.; Vishveshwara, S. Oligomeric protein structure networks: Insights into protein-protein interactions. BMC Bioinform. 2005, 6, 296.
2. Xia, Y.; Yu, H.; Jansen, R.; Seringhaus, M.; Baxter, S.; Greenbaum, D.; Zhao, H.; Gerstein, M. Analyzing cellular biochemistry in terms of molecular networks. Ann. Rev. Biochem. 2004, 73, 1051-1087.
3. Borroto-Escuela, D.O.; Agnati, L.F.; Fuxe, K.; Ciruela, F. Muscarinic acetylcholine receptor-interacting proteins (mAChRIPs): Targeting the receptorsome. Curr. Drug Targets 2012, 13, 53-71.
4. Borroto-Escuela, D.O.; Correia, P.A.; Romero-Fernandez, W.; Narvaez, M.; Fuxe, K.; Ciruela, F.; Garriga, P. Muscarinic receptor family interacting proteins: Role in receptor function. J. Neurosci. Methods 2011, 195, 161-169.
5. Choura, M.; Rebai, A. Application of computational approaches to study signalling networks of nuclear and Tyrosine kinase receptors. Biol. Direct 2010, 5, 58.
6. Barabasi, A.L.; Oltvai, Z.N. Network biology: Understanding the cell's functional organization. Nat. Rev. Genet. 2004, 5, 101-113.
7. Yook, S.H.; Oltvai, Z.N.; Barabasi, A.L. Functional and topological characterization of protein interaction networks. Proteomics 2004, 4, 928-942.
8. Chandra, N.; Padiadpu, J. Network approaches to drug discovery. Expert Opin. Drug Discov. 2013, 8, 7-20.
9. Perica, T.; Marsh, J.A.; Sousa, F.L.; Natan, E.; Colwell, L.J.; Ahnert, S.E.; Teichmann, S.A. The emergence of protein complexes: Quaternary structure, dynamics and allostery. Colworth Medal Lecture. Biochem. Soc. Trans. 2012, 40, 475-491.
10. Dixon, R.A.; Kobilka, B.K.; Strader, D.J.; Benovic, J.L.; Dohlman, H.G.; Frielle, T.; Bolanowski, M.A.; Bennett, C.D.; Rands, E.; Diehl, R.E.; et al. Cloning of the gene and cDNA for mammalian beta-adrenergic receptor and homology with rhodopsin. Nature 1986, 321, 75-79.
11. Fuxe, K.; Borroto-Escuela, D.O.; Romero-Fernandez, W.; Palkovits, M.; Tarakanov, A.O.; Ciruela, F.; Agnati, L.F. Moonlighting proteins and protein-protein interactions as neurotherapeutic targets in the G protein-coupled receptor field. Neuropsychopharmacology 2014, 39, 131-155.
12. Borroto-Escuela, D.O.; Romero-Fernandez, W.; Garriga, P.; Ciruela, F.; Narvaez, M.; Tarakanov, A.O.; Palkovits, M.; Agnati, L.F.; Fuxe, K. G protein-coupled receptor heterodimerization in the brain. Methods Enzymol. 2013, 521, 281-294.
13. Borroto-Escuela, D.O.; Romero-Fernandez, W.; Rivera, A.; van Craenenbroeck, K.; Tarakanov, A.O.; Agnati, L.F.; Fuxe, K. On the G protein-coupled receptor heteromers and their allosteric receptor-receptor interactions in the central nervous system: Focus on their role in pain modulation. Evid. Based Complent. Altern. Med. 2013, 2013, 563716.
14. Fuxe, K.; Borroto-Escuela, D.O.; Marcellino, D.; Romero-Fernandez, W.; Frankowska, M.; Guidolin, D.; Filip, M.; Ferraro, L.; Woods, A.S.; Tarakanov, A.; et al. GPCR heteromers and their allosteric receptor-receptor interactions. Curr. Med. Chem. 2012, 19, 356-363.
15. Borroto-Escuela, D.O.; Tarakanov, A.O.; Guidolin, D.; Ciruela, F.; Agnati, L.F.; Fuxe, K. Moonlighting characteristics of G protein-coupled receptors: Focus on receptor heteromers and relevance for neurodegeneration. IUBMB Life 2011, 63, 463-472.
16. Fuxe, K.; Marcellino, D.; Borroto-Escuela, D.O.; Frankowska, M.; Ferraro, L.; Guidolin, D.; Ciruela, F.; Agnati, L.F. The changing world of G protein-coupled receptors: From monomers to dimers and receptor mosaics with allosteric receptor-receptor interactions. J. Recept. Signal Transduct. Res. 2010, 30, 272-283.
17. Skieterska, K.; Duchou, J.; Lintermans, B.; van Craenenbroeck, K. Detection of G protein-coupled receptor (GPCR) dimerization by coimmunoprecipitation. Methods Cell Biol. 2013, 117, 323-340.
18. Van Craenenbroeck, K. GPCR oligomerization: Contribution to receptor biogenesis. In GPCR Signalling Complexes-Synthesis, Assembly, Trafficking and Specificity; Dupré, D.J., Hébert, T.E., Jockers, R., Eds.; Subcellular Biochemistry; Springer Netherlands: Dordrecht, The Netherland, 2012; Volume 63, pp. 43-65.
19. Agnati, L.F.; Fuxe, K.; Zini, I.; Lenzi, P.; Hokfelt, T. Aspects on receptor regulation and isoreceptor identification. Med. Biol. 1980, 58, 182-187.
20. Agnati, L.F.; Fuxe, K.; Zoli, M.; Rondanini, C.; Ogren, S.O. New vistas on synaptic plasticity: The receptor mosaic hypothesis of the engram. Med. Biol. 1982, 60, 183-190.
21. Fuxe, K.; Agnati, L.F.; Benfenati, F.; Celani, M.; Zini, I.; Zoli, M.; Mutt, V. Evidence for the existence of receptor-receptor interactions in the central nervous system. Studies on the regulation of monoamine receptors by neuropeptides. J. Neural. Transm. Suppl. 1983, 18, 165-179.
22. Fuxe, K.; Agnati, L.F.; Benfenati, F.; Cimmino, M.; Algeri, S.; Hokfelt, T.; Mutt, V. Modulation by cholecystokinins of 3H-spiroperidol binding in rat striatum: evidence for increased affinity and reduction in the number of binding sites. Acta Physiol. Scand. 1981, 113, 567-569.
23. Zoli, M.; Agnati, L.F.; Hedlund, P.B.; Li, X.M.; Ferre, S.; Fuxe, K. Receptor-receptor interactions as an integrative mechanism in nerve cells. Mol. Neurobiol. 1993, 7, 293-334.
24. Marshall, F.H.; Jones, K.A.; Kaupmann, K.; Bettler, B. GABAB receptors-The first 7TM heterodimers. Trends Pharmacol. Sci. 1999, 20, 396-399.
25. Marshall, F.H. Is the GABA B heterodimer a good drug target? J. Mol. Neurosci. 2005, 26, 169-176.
26. Gurevich, V.V.; Gurevich, E.V. How and why do GPCRs dimerize? Trends Pharmacol. Sci. 2008, 29, 234-240.
27. Gurevich, V.V.; Gurevich, E.V. GPCR monomers and oligomers: It takes all kinds. Trends Neurosci. 2008, 31, 74-81.
28. Fuxe, K.; Ferre, S.; Zoli, M.; Agnati, L.F. Integrated events in central dopamine transmission as analyzed at multiple levels. Evidence for intramembrane adenosine A2A/dopamine D2 and adenosine A1/dopamine D1 receptor interactions in the basal ganglia. Brain Res. Brain Res. Rev. 1998, 26, 258-273.
29. Franco, R.; Ferre, S.; Agnati, L.; Torvinen, M.; Gines, S.; Hillion, J.; Casado, V.; Lledo, P.; Zoli, M.; Lluis, C.; et al. Evidence for adenosine/dopamine receptor interactions: Indications for heteromerization. Neuropsychopharmacology 2000, 23, S50-S59.
30. Gines, S.; Hillion, J.; Torvinen, M.; le Crom, S.; Casado, V.; Canela, E.I.; Rondin, S.; Lew, J.Y.; Watson, S.; Zoli, M.; et al. Dopamine D1 and adenosine A1 receptors form functionally interacting heteromeric complexes. Proc. Natl. Acad. Sci. USA 2000, 97, 8606-8611.
31. Angers, S.; Salahpour, A.; Bouvier, M. Biochemical and biophysical demonstration of GPCR oligomerization in mammalian cells. Life Sci. 2001, 68, 2243-2250.
32. Angers, S.; Salahpour, A.; Joly, E.; Hilairet, S.; Chelsky, D.; Dennis, M.; Bouvier, M. Detection of beta 2-adrenergic receptor dimerization in living cells using bioluminescence resonance energy transfer (BRET). Proc. Natl. Acad. Sci. USA 2000, 97, 3684-3689.
33. Hebert, T.E.; Loisel, T.P.; Adam, L.; Ethier, N.; Onge, S.S.; Bouvier, M. Functional rescue of a constitutively desensitized beta2AR through receptor dimerization. Biochem. J. 1998, 330, 287-293.
34. Dean, M.K.; Higgs, C.; Smith, R.E.; Bywater, R.P.; Snell, C.R.; Scott, P.D.; Upton, G.J.; Howe, T.J.; Reynolds, C.A. Dimerization of G protein-coupled receptors. J. Med. Chem. 2001, 44, 4595-4614.
35. Gouldson, P.R.; Higgs, C.; Smith, R.E.; Dean, M.K.; Gkoutos, G.V.; Reynolds, C.A. Dimerization and domain swapping in G protein-coupled receptors: A computational study. Neuropsychopharmacology 2000, 23, S60-S77.
36. Gouldson, P.R.; Snell, C.R.; Bywater, R.P.; Higgs, C.; Reynolds, C.A. Domain swapping in G-protein coupled receptor dimers. Protein Eng. 1998, 11, 1181-1193.
37. Devi, L.A. Heterodimerization of G protein-coupled receptors: Pharmacology, signaling and trafficking. Trends Pharmacol. Sci. 2001, 22, 532-537.
38. Kenakin, T. Drug efficacy at G protein-coupled receptors. Ann. Rev. Pharmacol. Toxicol. 2002, 42, 349-379.
39. Lee, S.P.; Xie, Z.; Varghese, G.; Nguyen, T.; O'Dowd, B.F.; George, S.R. Oligomerization of dopamine and serotonin receptors. Neuropsychopharmacology 2000, 23, S32-S40.
40. Xie, Z.; Lee, S.P.; O'Dowd, B.F.; George, S.R. Serotonin 5-HT1B and 5-HT1D receptors form homodimers when expressed alone and heterodimers when co-expressed. FEBS Lett. 1999, 456, 63-67.
41. Zeng, F.; Wess, J. Molecular aspects of muscarinic receptor dimerization. Neuropsychopharmacology 2000, 23, S19-S31.
42. Overton, M.C.; Blumer, K.J. G protein-coupled receptors function as oligomers in vivo. Curr. Biol. 2000, 10, 341-344.
43. Bockaert, J.; Pin, J.P. Molecular tinkering of G protein-coupled receptors: An evolutionary success. EMBO J. 1999, 18, 1723-1729.
44. Portoghese, P.S. From models to molecules: Opioid receptor dimers, bivalent ligands, and selective opioid receptor probes. J. Med. Chem. 2001, 44, 2259-2269.
45. Waldhoer, M.; Fong, J.; Jones, R.M.; Lunzer, M.M.; Sharma, S.K.; Kostenis, E.; Portoghese, P.S.; Whistler, J.L. A heterodimer-selective agonist shows in vivo relevance of G protein-coupled receptor dimers. Proc. Natl. Acad. Sci. USA 2005, 102, 9050-9055.
46. Stockton, S.D., Jr.; Devi, L.A. Functional relevance of mu-delta opioid receptor heteromerization: A role in novel signaling and implications for the treatment of addiction disorders: From a symposium on new concepts in mu-opioid pharmacology. Drug Alcohol Depend. 2012, 121, 167-172.
47. Perreault, M.L.; Hasbi, A.; O'Dowd, B.F.; George, S.R. Heteromeric dopamine receptor signaling complexes: Emerging neurobiology and disease relevance. Neuropsychopharmacology 2014, 39, 156-168.
48. Pou, C.; Mannoury la Cour, C.; Stoddart, L.A.; Millan, M.J.; Milligan, G. Functional homomers and heteromers of dopamine D2L and D3 receptors co-exist at the cell surface. J. Biol. Chem. 2012, 287, 8864-8878.
49. Wang, M.; Wong, A.H.; Liu, F. Interactions between NMDA and dopamine receptors: A potential therapeutic target. Brain Res. 2012, 1476, 154-163.
50. Satake, H.; Matsubara, S.; Aoyama, M.; Kawada, T.; Sakai, T. GPCR Heterodimerization in the Reproductive System: Functional regulation and implication for biodiversity. Front. Endocrinol. 2013, 4, 100.
51. Suzuki, T.; Namba, K.; Mizuno, N.; Nakata, H. Hetero-oligomerization and specificity changes of G protein-coupled purinergic receptors: Novel insight into diversification of signal transduction. Methods Enzymol. 2013, 521, 239-257.
52. Borroto-Escuela, D.O.; Flajolet, M.; Agnati, L.F.; Greengard, P.; Fuxe, K. Bioluminescence resonance energy transfer methods to study G protein-coupled receptor-receptor tyrosine kinase heteroreceptor complexes. Methods Cell Biol. 2013, 117, 141-164.
53. Fernandez-Duenas, V.; Llorente, J.; Gandia, J.; Borroto-Escuela, D.O.; Agnati, L.F.; Tasca, C.I.; Fuxe, K.; Ciruela, F. Fluorescence resonance energy transfer-based technologies in the study of protein-protein interactions at the cell surface. Methods 2012, 57, 467-472.
54. Achour, L.; Kamal, M.; Jockers, R.; Marullo, S. Using quantitative BRET to assess G protein-coupled receptor homo-and heterodimerization. Methods Mol. Biol. 2011, 756, 183-200.
55. Lohse, M.J.; Nuber, S.; Hoffmann, C. Fluorescence/bioluminescence resonance energy transfer techniques to study G protein-coupled receptor activation and signaling. Pharmacol. Rev. 2012, 64, 299-336.
56. Goupil, E.; Laporte, S.A.; Hebert, T.E. A simple method to detect allostery in GPCR dimers. Methods Cell Biol. 2013, 117, 165-179.
57. Hink, M.A.; Postma, M. Monitoring receptor oligomerization by line-scan fluorescence cross-correlation spectroscopy. Methods Cell Biol. 2013, 117, 197-212.
58. Herrick-Davis, K.; Grinde, E.; Cowan, A.; Mazurkiewicz, J.E. Fluorescence correlation spectroscopy analysis of serotonin, adrenergic, muscarinic, and dopamine receptor dimerization: the oligomer number puzzle. Mol. Pharmacol. 2013, 84, 630-642.
59. Kuhn, C.; Bufe, B.; Batram, C.; Meyerhof, W. Oligomerization of TAS2R bitter taste receptors. Chem. Senses 2010, 35, 395-406.
60. GPCR-HetNet. Available online: http://www.iiia.csic.es/~ismel/GPCR-Nets/index.html (accessed on 11 May 2014).
61. Jassal, B.; Jupe, S.; Caudy, M.; Birney, E.; Stein, L.; Hermjakob, H.; D'Eustachio, P. The systematic annotation of the three main GPCR families in Reactome. Database (Oxford) 2010, 2010, baq018.
62. Attwood, T.K.; Findlay, J.B. Fingerprinting G protein-coupled receptors. Protein Eng. 1994, 7, 195-203.
63. Cardoso, J.C.; Pinto, V.C.; Vieira, F.A.; Clark, M.S.; Power, D.M. Evolution of secretin family GPCR members in the metazoa. BMC Evol. Biol. 2006, 6, 108.
64. Sukhwal, A.; Sowdhamini, R. Oligomerisation status and evolutionary conservation of interfaces of protein structural domain superfamilies. Mol. Biosyst. 2013, 9, 1652-1661.
65. Havlickova, M.; Prezeau, L.; Duthey, B.; Bettler, B.; Pin, J.P.; Blahos, J. The intracellular loops of the GB2 subunit are crucial for G-protein coupling of the heteromeric gamma-aminobutyrate B receptor. Mol. Pharmacol. 2002, 62, 343-350.
66. Delprato, A. Topological and functional properties of the small GTPases protein interaction network. PLoS One 2012, 7, e44882.
67. Agnati, L.F.; Guidolin, D.; Albertin, G.; Trivello, E.; Ciruela, F.; Genedani, S.; Tarakanov, A.; Fuxe, K. An integrated view on the role of receptor mosaics at perisynaptic level: Focus on adenosine A(2A), dopamine D(2), cannabinoid CB(1), and metabotropic glutamate mGlu(5) receptors. J. Recept. Signal Transduct. Res. 2010, 30, 355-369.
68. Cabello, N.; Gandia, J.; Bertarelli, D.C.; Watanabe, M.; Lluis, C.; Franco, R.; Ferre, S.; Lujan, R.; Ciruela, F. Metabotropic glutamate type 5, dopamine D2 and adenosine A2a receptors form higher-order oligomers in living cells. J. Neurochem. 2009, 109, 1497-1507.
69. Navarro, G.; Carriba, P.; Gandia, J.; Ciruela, F.; Casado, V.; Cortes, A.; Mallol, J.; Canela, E.I.; Lluis, C.; Franco, R. Detection of heteromers formed by cannabinoid CB1, dopamine D2, and adenosine A2A G protein-coupled receptors by combining bimolecular fluorescence complementation and bioluminescence energy transfer. Sci. World J. 2008, 8, 1088-1097.
70. Carriba, P.; Navarro, G.; Ciruela, F.; Ferre, S.; Casado, V.; Agnati, L.; Cortes, A.; Mallol, J.; Fuxe, K.; Canela, E.I.; et al. Detection of heteromerization of more than two proteins by sequential BRET-FRET. Nat. Methods 2008, 5, 727-733.
71. Borroto-Escuela, D.O.; Narvaez, M.; Marcellino, D.; Parrado, C.; Narvaez, J.A.; Tarakanov, A.O.; Agnati, L.F.; Diaz-Cabiale, Z.; Fuxe, K. Galanin receptor-1 modulates 5-hydroxtryptamine-1A signaling via heterodimerization. Biochem. Biophys. Res. Commun. 2010, 393, 767-772.
72. Han, J.D.; Bertin, N.; Hao, T.; Goldberg, D.S.; Berriz, G.F.; Zhang, L.V.; Dupuy, D.; Walhout, A.J.; Cusick, M.E.; Roth, F.P.; et al. Evidence for dynamically organized modularity in the yeast protein-protein interaction network. Nature 2004, 430, 88-93.
73. Albert, R.; Jeong, H.; Barabasi, A.L. Error and attack tolerance of complex networks. Nature 2000, 406, 378-382.
74. Wuchty, S.; Almaas, E. Peeling the yeast protein network. Proteomics 2005, 5, 444-449.
75. Vallabhajosyula, R.R.; Chakravarti, D.; Lutfeali, S.; Ray, A.; Raval, A. Identifying hubs in protein interaction networks. PLoS One 2009, 4, e5344.
76. Batada, N.N.; Reguly, T.; Breitkreutz, A.; Boucher, L.; Breitkreutz, B.J.; Hurst, L.D.; Tyers, M. Stratus not altocumulus: A new view of the yeast protein interaction network. PLoS Biol. 2006, 4, e317.
77. Ekman, D.; Light, S.; Bjorklund, A.K.; Elofsson, A. What properties characterize the hub proteins of the protein-protein interaction network of Saccharomyces cerevisiae? Genome Biol. 2006, 7, R45.
78. Tarakanov, A.O.; Fuxe, K.G.; Borroto-Escuela, D.O. Integrin triplets of marine sponges in human D2 receptor heteromers. J. Recept. Signal Transduct. Res. 2012, 32, 202-208.
79. Tarakanov, A.O.; Fuxe, K.G. Triplet puzzle: Homologies of receptor heteromers. J. Mol. Neurosci. 2010, 41, 294-303.
80. Tarakanov, A.O.; Fuxe, K.G. The triplet puzzle of homologies in receptor heteromers exists also in other types of protein-protein interactions. J. Mol. Neurosci. 2011, 44, 173-177.
81. Tarakanov, A.O.; Fuxe, K.G.; Borroto-Escuela, D.O. On the origin of the triplet puzzle of homologies in receptor heteromers: Toll-like receptor triplets in different types of receptors. J. Neural Transm. 2012, 119, 517-523.
82. Tarakanov, A.O.; Fuxe, K.G.; Borroto-Escuela, D.O. On the origin of the triplet puzzle of homologies in receptor heteromers: immunoglobulin triplets in different types of receptors. J. Mol. Neurosci. 2012, 46, 616-621.
83. Fuxe, K.; Marcellino, D.; Woods, A.S.; Giuseppina, L.; Antonelli, T.; Ferraro, L.; Tanganelli, S.; Agnati, L.F. Integrated signaling in heterodimers and receptor mosaics of different types of GPCRs of the forebrain: Relevance for schizophrenia. J. Neural Transm. 2009, 116, 923-939.
84. STRING. Available online: http://string-db.org/ (accessed on 11 May 2014).
85. Cytoscape, Version 2.8.2. Available online: http://www.cytoscape.org/ (accessed on 11 May 2014).
86. Zhu, X.; Gerstein, M.; Snyder, M. Getting connected: Analysis and principles of biological networks. Genes Dev. 2007, 21, 1010-1024.
87. Molecular Complex Detection (MCODE), Version 1.2. Available online: http://baderlab.org/ Software/MCODE (accessed on 11 May 2014).