The plasticity of the 7TMR signaling machinery and the search for pharmacological selectivity

Current Pharmaceutical Design

Volumn 18, Issue 2, 2012, Pages 145-160

  Flordellis, Christodoulos S ^a  

^a UNIVERSITY OF PATRAS   (Greece)

Author keywords

7TMR oligomerization; 7TMR signaling; Drug selectivity; Fingolimod; GPCR compartmentalization; Pharmacochaperones; Receptor plasticity

Indexed keywords

CHAPERONE; DIMER; FINGOLIMOD; GUANINE NUCLEOTIDE BINDING PROTEIN; MEMBRANE RECEPTOR; PARATHYROID HORMONE RECEPTOR; PHARMACOCHAPERONE; PROTEIN INHIBITOR; PROTEIN TYROSINE KINASE; SEVEN TRANSMEMBRANE RECEPTOR; SEVEN TRANSMEMBRANE RECEPTOR AGONIST; THYROTROPIN RECEPTOR; UNCLASSIFIED DRUG;

ALLOSTERISM; ARTICLE; CAVEOLA; CELL COMPARTMENTALIZATION; CELL MEMBRANE; CELL MIGRATION; CELLULAR DISTRIBUTION; DESENSITIZATION; DRUG DESIGN; DRUG EFFICACY; DRUG MECHANISM; DRUG SELECTIVITY; DRUG TARGETING; ENDOCYTOSIS; FLUORESCENCE RESONANCE ENERGY TRANSFER; HUMAN; INTERNALIZATION; INTRACELLULAR SIGNALING; LIGAND BINDING; LIPID MEMBRANE; LIPID RAFT; MACHINE; NONHUMAN; OLIGOMERIZATION; PRIORITY JOURNAL; PROTEIN ASSEMBLY; PROTEIN FOLDING; RECEPTOR OCCUPANCY; SIGNAL TRANSDUCTION; STRUCTURAL PLASTICITY;

ALLOSTERIC REGULATION; ANIMALS; CELL MEMBRANE; DRUG DESIGN; GTP-BINDING PROTEINS; HUMANS; LIGANDS; MEMBRANE MICRODOMAINS; PROTEIN BINDING; PROTEIN CONFORMATION; RECEPTORS, G-PROTEIN-COUPLED; SIGNAL TRANSDUCTION;

EID: 84856470106     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/138161212799040556     Document Type: Article

References (125)

1. Limbird LE. The receptor concept: a continuing evolution. Mol Interv 2004; 4: 326-36.
2. Kenakin T. New concepts in drug discovery: collateral efficacy and permissive antagonism. Nat Rev Drug Discov 2005; 4: 919-27.
3. Kholodenko BN. Cell-signalling dynamics in time and space. Nat Rev Mol Cell Biol 2006; 7: 165-76.
4. Keov P, Sexton PM, Christopoulos A. Allosteric modulation of G protein-coupled receptors: a pharmacological perspective. Neuropharmacology 2011; 60: 24-35.
5. Kenakin TP. Ligand detection in the allosteric world. J Biomol Screen 2010; 15: 119-30.
6. Kenakin T, Miller LJ. Seven transmembrane receptors as shapeshifting proteins: the impact of allosteric modulation and functional selectivity on new drug discovery. Pharmacol Rev 2010; 62: 265-304.
7. Kobilka BK, Deupi X. Conformational complexity of G-proteincoupled receptors. Trends Pharmacol Sci 2007; 28: 397-406.
8. Leff P. The two-state model of receptor activation. Trends Pharmacol Sci 1995; 16: 89-97.
9. Bosshard HR. Molecular recognition by induced fit: how fit is the concept? News Physiol Sci 2001; 16: 171-3.
10. Insel PA. Location, location, location. Trends Endocrinol Metab 2003; 14: 100-2.
11. Patel CB, Noor N, Rockman HA. Functional selectivity in adrenergic and angiotensin signaling systems. Mol Pharmacol 2010; 78: 983-92.
12. Drake MT, Violin JD, Whalen EJ, Wisler JW, Shenoy SK, Lefkowitz RJ. beta-arrestin-biased agonism at the beta2-adrenergic receptor. J Biol Chem 2008; 283: 5669-76.
13. James LC, Tawfik DS. Conformational diversity and protein evolution--a 60-year-old hypothesis revisited. Trends Biochem Sci 2003; 28: 361-8.
14. Burgen AS. Conformational changes and drug action. Fed Proc 1981; 40: 2723-8.
15. Chini B, Parenti M. G-protein coupled receptors in lipid rafts and caveolae: how, when and why do they go there? J Mol Endocrinol 2004; 32: 325-38.
16. Marshall CJ. Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation. Cell 1995; 80: 179-85.
17. Karkoulias G, Mastrogianni O, Lymperopoulos A, Paris H, Flordellis C. alpha(2)-Adrenergic receptors activate MAPK and Akt through a pathway involving arachidonic acid metabolism by cytochrome P450-dependent epoxygenase, matrix metalloproteinase activation and subtype-specific transactivation of EGFR. Cell Signal 2006; 18: 729-39.
18. Steinberg SF, Brunton LL. Compartmentation of G protein-coupled signaling pathways in cardiac myocytes. Annu Rev Pharmacol Toxicol 2001; 41: 751-73.
19. Kenakin T. Collateral efficacy in drug discovery: taking advantage of the good (allosteric) nature of 7TM receptors. Trends Pharmacol Sci 2007; 28: 407-15.
20. Azzi M, Charest PG, Angers S, Rousseau G, Kohout T, Bouvier M, Pineyro G. Beta-arrestin-mediated activation of MAPK by inverse agonists reveals distinct active conformations for G proteincoupled receptors. Proc Natl Acad Sci U S A 2003; 100: 11406-11.
21. Galandrin S, Bouvier M. Distinct signaling profiles of beta1 and beta2 adrenergic receptor ligands toward adenylyl cyclase and mitogen-activated protein kinase reveals the pluridimensionality of efficacy. Mol Pharmacol 2006; 70: 1575-84.
22. Galandrin S, Oligny-Longpre G, Bouvier M. The evasive nature of drug efficacy: implications for drug discovery. Trends Pharmacol Sci 2007; 28: 423-30.
23. Kohout TA, Nicholas SL, Perry SJ, Reinhart G, Junger S, Struthers RS. Differential desensitization, receptor phosphorylation, betaarrestin recruitment, and ERK1/2 activation by the two endogenous ligands for the CC chemokine receptor 7. J Biol Chem 2004; 279: 23214-22.
24. Zidar DA, Violin JD, Whalen EJ, Lefkowitz RJ. Selective engagement of G protein coupled receptor kinases (GRKs) encodes distinct functions of biased ligands. Proc Natl Acad Sci U S A 2009; 106: 9649-54.
25. Calebiro D, Nikolaev VO, Persani L, Lohse MJ. Signaling by internalized G-protein-coupled receptors. Trends Pharmacol Sci 2010; 31: 221-8.
26. Rajagopal S, Rajagopal K, Lefkowitz RJ. Teaching old receptors new tricks: biasing seven-transmembrane receptors. Nat Rev Drug Discov 2010; 9: 373-86.
27. Rajagopal K, Lefkowitz RJ, Rockman HA. When 7 transmembrane receptors are not G protein-coupled receptors. J Clin Invest 2005; 115: 2971-4.
28. Patel HH, Murray F, Insel PA. G-protein-coupled receptorsignaling components in membrane raft and caveolae microdomains. Handb Exp Pharmacol 2008: 167-84.
29. Tsunoda S, Sierralta J, Sun Y, et al. A multivalent PDZ-domain protein assembles signalling complexes in a G-protein-coupled cascade. Nature 1997; 388: 243-9.
30. Marguet D, Lenne PF, Rigneault H, He HT. Dynamics in the plasma membrane: how to combine fluidity and order. EMBO J 2006; 25: 3446-57.
31. Pike LJ. The challenge of lipid rafts. J Lipid Res 2009; 50 Suppl: S323-8.
32. Nobles M, Benians A, Tinker A. Heterotrimeric G proteins precouple with G protein-coupled receptors in living cells. Proc Natl Acad Sci U S A 2005; 102: 18706-11.
33. Agnati LF, Guidolin D, Leo G, et al. Role of cooperativity in protein folding and protein mosaic assemblage relevance for protein conformational diseases. Curr Protein Pept Sci 2007; 8: 460-70.
34. Pike LJ. Rafts defined: a report on the Keystone Symposium on Lipid Rafts and Cell Function. J Lipid Res 2006; 47: 1597-8.
35. Simons K, Ehehalt R. Cholesterol, lipid rafts, and disease. J Clin Invest 2002; 110: 597-603.
36. Simons K, Toomre D. Lipid rafts and signal transduction. Nat Rev Mol Cell Biol 2000; 1: 31-9.
37. Hnasko R, Lisanti MP. The biology of caveolae: lessons from caveolin knockout mice and implications for human disease. Mol Interv 2003; 3: 445-64.
38. Couet J, Li S, Okamoto T, Ikezu T, Lisanti MP. Identification of peptide and protein ligands for the caveolin-scaffolding domain. Implications for the interaction of caveolin with caveolaeassociated proteins. J Biol Chem 1997; 272: 6525-33.
39. Insel PA, Head BP, Patel HH, Roth DM, Bundey RA, Swaney JS. Compartmentation of G-protein-coupled receptors and their signalling components in lipid rafts and caveolae. Biochem Soc Trans 2005; 33: 1131-4.
40. Razani B, Woodman SE, Lisanti MP. Caveolae: from cell biology to animal physiology. Pharmacol Rev 2002; 54: 431-67.
41. Zacharias DA, Violin JD, Newton AC, Tsien RY. Partitioning of lipid-modified monomeric GFPs into membrane microdomains of live cells. Science 2002; 296: 913-6.
42. Miljan EA, Bremer EG. Regulation of growth factor receptors by gangliosides. Sci STKE 2002; 2002: re15.
43. Oh P, Schnitzer JE. Segregation of heterotrimeric G proteins in cell surface microdomains. G(q) binds caveolin to concentrate in caveolae, whereas G(i) and G(s) target lipid rafts by default. Mol Biol Cell 2001; 12: 685-98.
44. Ostrom RS, Gregorian C, Drenan RM, Xiang Y, Regan JW, Insel PA. Receptor number and caveolar co-localization determine receptor coupling efficiency to adenylyl cyclase. J Biol Chem 2001; 276: 42063-9.
45. Rimoldi V, Reversi A, Taverna E, et al. Oxytocin receptor elicits different EGFR/MAPK activation patterns depending on its localization in caveolin-1 enriched domains. Oncogene 2003; 22: 6054-60.
46. Ushio-Fukai M, Griendling KK, Becker PL, Hilenski L, Halleran S, Alexander RW. Epidermal growth factor receptor transactivation by angiotensin II requires reactive oxygen species in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 2001; 21: 489-95.
47. Feron O, Kelly RA. The caveolar paradox: suppressing, inducing, and terminating eNOS signaling. Circ Res 2001; 88: 129-31.
48. Sabourin T, Bastien L, Bachvarov DR, Marceau F. Agonistinduced translocation of the kinin B(1) receptor to caveolae-related rafts. Mol Pharmacol 2002; 61: 546-53.
49. Ostrom RS, Insel PA. The evolving role of lipid rafts and caveolae in G protein-coupled receptor signaling: implications for molecular pharmacology. Br J Pharmacol 2004; 143: 235-45.
50. Pierce KL, Premont RT, Lefkowitz RJ. Seven-transmembrane receptors. Nat Rev Mol Cell Biol 2002; 3: 639-50.
51. Shenoy SK, Lefkowitz RJ. Multifaceted roles of beta-arrestins in the regulation of seven-membrane-spanning receptor trafficking and signalling. Biochem J 2003; 375: 503-15.
52. Goodman OB, Jr., Krupnick JG, Santini F, et al. Beta-arrestin acts as a clathrin adaptor in endocytosis of the beta2-adrenergic receptor. Nature 1996; 383: 447-50.
53. Miaczynska M, Pelkmans L, Zerial M. Not just a sink: endosomes in control of signal transduction. Curr Opin Cell Biol 2004; 16: 400-6.
54. Baass PC, Di Guglielmo GM, Authier F, Posner BI, Bergeron JJ. Compartmentalized signal transduction by receptor tyrosine kinases. Trends Cell Biol 1995; 5: 465-70.
55. Jalink K, Moolenaar WH. G protein-coupled receptors: the inside story. Bioessays 2010; 32: 13-6.
56. Gobeil F, Fortier A, Zhu T, et al. G-protein-coupled receptors signalling at the cell nucleus: an emerging paradigm. Can J Physiol Pharmacol 2006; 84: 287-97.
57. Hanyaloglu AC, von Zastrow M. Regulation of GPCRs by endocytic membrane trafficking and its potential implications. Annu Rev Pharmacol Toxicol 2008; 48: 537-68.
58. Miaczynska M, Bar-Sagi D. Signaling endosomes: seeing is believing. Curr Opin Cell Biol 2010; 22: 535-40.
59. von Zastrow M, Sorkin A. Signaling on the endocytic pathway. Curr Opin Cell Biol 2007; 19: 436-45.
60. Sorkin A, von Zastrow M. Endocytosis and signalling: intertwining molecular networks. Nat Rev Mol Cell Biol 2009; 10: 609-22.
61. Kelly EE, Horgan CP, McCaffrey MW, Young P. The role of endosomal-recycling in long-term potentiation. Cell Mol Life Sci 2011; 68: 185-94.
62. Robben JH, Kortenoeven ML, Sze M, et al. Intracellular activation of vasopressin V2 receptor mutants in nephrogenic diabetes insipidus by nonpeptide agonists. Proc Natl Acad Sci U S A 2009; 106: 12195-200.
63. Nikolaev VO, Gambaryan S, Lohse MJ. Fluorescent sensors for rapid monitoring of intracellular cGMP. Nat Methods 2006; 3: 23-5.
64. Calebiro D, Nikolaev VO, Lohse MJ. Imaging of persistent cAMP signaling by internalized G protein-coupled receptors. J Mol Endocrinol 2010; 45: 1-8.
65. McDonald PH, Chow CW, Miller WE, et al. Beta-arrestin 2: a receptor-regulated MAPK scaffold for the activation of JNK3. Science 2000; 290: 1574-7.
66. Calebiro D, Nikolaev VO, Gagliani MC, et al. Persistent cAMPsignals triggered by internalized G-protein-coupled receptors. PLoS Biol 2009; 7: e1000172.
67. Yang M, He RL, Benovic JL, Ye RD. beta-Arrestin1 interacts with the G-protein subunits beta1gamma2 and promotes beta1gamma2-dependent Akt signalling for NF-kappaB activation. Biochem J 2009; 417: 287-96.
68. Feinstein TN, Wehbi VL, Ardura JA, et al. Retromer terminates the generation of cAMP by internalized PTH receptors. Nat Chem Biol 2011; 7: 278-84.
69. Norwood SJ, Shaw DJ, Cowieson NP, Owen DJ, Teasdale RD, Collins BM. Assembly and solution structure of the core retromer protein complex. Traffic 2011; 12: 56-71.
70. Gould GW, Lippincott-Schwartz J. New roles for endosomes: from vesicular carriers to multi-purpose platforms. Nat Rev Mol Cell Biol 2009; 10: 287-92.
71. US Food and Drugs Administration. FDA approves first oral drug to reduce MS relapses. 2010. Available at: http://www.fda.gov/News Events/Newsroom/Press Announcements/ ucm226755.htm.Accessed December 27 2010
72. Matloubian M, Lo CG, Cinamon G, et al. Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1. Nature 2004; 427: 355-60.
73. Kappos L, Radue EW, O'Connor P, et al. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med 2010; 362: 387-401.
74. Nicholas R, Giannetti P, Alsanousi A, Friede T, Muraro PA. Development of oral immunomodulatory agents in the management of multiple sclerosis. Drug Des Devel Ther 2011; 5: 255-74.
75. Cohen JA, Barkhof F, Comi G, et al. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med 2010; 362: 402-15.
76. Su W, Liu Y, Xia Y, Hong Z, Li J. Conserved endoplasmic reticulum-associated degradation system to eliminate mutated receptor-like kinases in Arabidopsis. Proc Natl Acad Sci U S A 2011; 108: 870-5.
77. Bernier V, Lagace M, Bichet DG, Bouvier M. Pharmacological chaperones: potential treatment for conformational diseases. Trends Endocrinol Metab 2004; 15: 222-8.
78. Morello JP, Salahpour A, Laperriere A, et al. Pharmacological chaperones rescue cell-surface expression and function of misfolded V2 vasopressin receptor mutants. J Clin Invest 2000; 105: 887-95.
79. Jean-Alphonse F, Perkovska S, Frantz MC, et al. Biased agonist pharmacochaperones of the AVP V2 receptor may treat congenital nephrogenic diabetes insipidus. J Am Soc Nephrol 2009; 20: 2190-203.
80. Robben JH, Sze M, Knoers NV, Deen PM. Functional rescue of vasopressin V2 receptor mutants in MDCK cells by pharmacochaperones: relevance to therapy of nephrogenic diabetes insipidus. Am J Physiol Renal Physiol 2007; 292: F253-60.
81. Bernier V, Morello JP, Zarruk A, et al. Pharmacologic chaperones as a potential treatment for X-linked nephrogenic diabetes insipidus. J Am Soc Nephrol 2006; 17: 232-43.
82. Los EL, Deen PM, Robben JH. Potential of nonpeptide antagonists to rescue vasopressin V2 receptor mutants for the treatment of Xlinked nephrogenic diabetes insipidus. J Neuroendocrinol 2010; 22: 393-9.
83. Engstrom M, Savola JM, Wurster S. Differential efficacies of somatostatin receptor agonists for G-protein activation and desensitization of somatostatin receptor subtype 4-mediated responses. J Pharmacol Exp Ther 2006; 316: 1262-8.
84. Whorton MR, Bokoch MP, Rasmussen SG, et al. A monomeric G protein-coupled receptor isolated in a high-density lipoprotein particle efficiently activates its G protein. Proc Natl Acad Sci U S A 2007; 104: 7682-7.
85. Kuszak AJ, Pitchiaya S, Anand JP, Mosberg HI, Walter NG, Sunahara RK. Purification and functional reconstitution of monomeric mu-opioid receptors: allosteric modulation of agonist binding by Gi2. J Biol Chem 2009; 284: 26732-41.
86. Palczewski K. Oligomeric forms of G protein-coupled receptors (GPCRs). Trends Biochem Sci 2010; 35: 595-600.
87. Lohse MJ. Dimerization in GPCR mobility and signaling. Curr Opin Pharmacol 2010; 10: 53-8.
88. Agnati LF, Leo G, Genedani S, et al. Structural plasticity in Gprotein coupled receptors as demonstrated by the allosteric actions of homocysteine and computer-assisted analysis of disordered domains. Brain Res Rev 2008; 58: 459-74.
89. Terrillon S, Bouvier M. Roles of G-protein-coupled receptor dimerization. EMBO Rep 2004; 5: 30-4.
90. Bouvier M. Oligomerization of G-protein-coupled transmitter receptors. Nat Rev Neurosci 2001; 2: 274-86.
91. Ferre S, Baler R, Bouvier M, et al. Building a new conceptual framework for receptor heteromers. Nat Chem Biol 2009; 5: 131-4.
92. Fuxe K, Marcellino D, Leo G, Agnati LF. Molecular integration via allosteric interactions in receptor heteromers. A working hypothesis. Curr Opin Pharmacol 2010; 10: 14-22.
93. Limbird LE, Lefkowitz RJ. Negative cooperativity among betaadrenergic receptors in frog erythrocyte membranes. J Biol Chem 1976; 251: 5007-14.
94. Petaja-Repo UE, Hogue M, Laperriere A, Walker P, Bouvier M. Export from the endoplasmic reticulum represents the limiting step in the maturation and cell surface expression of the human delta opioid receptor. J Biol Chem 2000; 275: 13727-36.
95. Marshall FH, Jones KA, Kaupmann K, Bettler B. GABAB receptors-the first 7TM heterodimers. Trends Pharmacol Sci 1999; 20: 396-9.
96. Minneman KP. Heterodimerization and surface localization of G protein coupled receptors. Biochem Pharmacol 2007; 73: 1043-50.
97. Gines S, Hillion J, Torvinen M, et al. Dopamine D1 and adenosine A1 receptors form functionally interacting heteromeric complexes. Proc Natl Acad Sci U S A 2000; 97: 8606-11.
98. Margeta-Mitrovic M, Jan YN, Jan LY. A trafficking checkpoint controls GABA(B) receptor heterodimerization. Neuron 2000; 27: 97-106.
99. Dorsch S, Klotz KN, Engelhardt S, Lohse MJ, Bunemann M. Analysis of receptor oligomerization by FRAP microscopy. Nat Methods 2009; 6: 225-30.
100. Fonseca JM, Lambert NA. Instability of a class a G protein-coupled receptor oligomer interface. Mol Pharmacol 2009; 75: 1296-9.
101. Fung JJ, Deupi X, Pardo L, et al. Ligand-regulated oligomerization of beta(2)-adrenoceptors in a model lipid bilayer. EMBO J 2009; 28: 3315-28.
102. Tateyama M, Abe H, Nakata H, Saito O, Kubo Y. Ligand-induced rearrangement of the dimeric metabotropic glutamate receptor 1alpha. Nat Struct Mol Biol 2004; 11: 637-42.
103. Vilardaga JP, Nikolaev VO, Lorenz K, Ferrandon S, Zhuang Z, Lohse MJ. Conformational cross-talk between alpha2A-adrenergic and mu-opioid receptors controls cell signaling. Nat Chem Biol 2008; 4: 126-31.
104. Hlavackova V, Goudet C, Kniazeff J, et al. Evidence for a single heptahelical domain being turned on upon activation of a dimeric GPCR. EMBO J 2005; 24: 499-509.
105. Damian M, Martin A, Mesnier D, Pin JP, Baneres JL. Asymmetric conformational changes in a GPCR dimer controlled by G-proteins. EMBO J 2006; 25: 5693-702.
106. Kniazeff J, Bessis AS, Maurel D, Ansanay H, Prezeau L, Pin JP. Closed state of both binding domains of homodimeric mGlu receptors is required for full activity. Nat Struct Mol Biol 2004; 11: 706-13.
107. Mellado M, Vila-Coro AJ, Martinez C, Rodriguez-Frade JM. Receptor dimerization: a key step in chemokine signaling. Cell Mol Biol (Noisy-le-grand) 2001; 47: 575-82.
108. George SR, Fan T, Xie Z, et al. Oligomerization of mu-and deltaopioid receptors. Generation of novel functional properties. J Biol Chem 2000; 275: 26128-35.
109. Hamm HE. How activated receptors couple to G proteins. Proc Natl Acad Sci U S A 2001; 98: 4819-21.
110. Han Y, Moreira IS, Urizar E, Weinstein H, Javitch JA. Allosteric communication between protomers of dopamine class A GPCR dimers modulates activation. Nat Chem Biol 2009; 5: 688-95.
111. Gurevich VV, Gurevich EV. How and why do GPCRs dimerize? Trends Pharmacol Sci 2008; 29: 234-40.
112. Guo W, Urizar E, Kralikova M, et al. Dopamine D2 receptors form higher order oligomers at physiological expression levels. EMBO J 2008; 27: 2293-304.
113. Woods AS, Ferre S. Amazing stability of the arginine-phosphate electrostatic interaction. J Proteome Res 2005; 4: 1397-402.
114. Fuxe K, Ferre S, Genedani S, Franco R, Agnati LF. Adenosine receptor-dopamine receptor interactions in the basal ganglia and their relevance for brain function. Physiol Behav 2007; 92: 210-7.
115. Fiorentini C, Busi C, Gorruso E, Gotti C, Spano P, Missale C. Reciprocal regulation of dopamine D1 and D3 receptor function and trafficking by heterodimerization. Mol Pharmacol 2008; 74: 59-69.
116. Stanasila L, Perez JB, Vogel H, Cotecchia S. Oligomerization of the alpha 1a-and alpha 1b-adrenergic receptor subtypes. Potential implications in receptor internalization. J Biol Chem 2003; 278: 40239-51.
117. Lavoie C, Mercier JF, Salahpour A, et al. Beta 1/beta 2-adrenergic receptor heterodimerization regulates beta 2-adrenergic receptor internalization and ERK signaling efficacy. J Biol Chem 2002; 277: 35402-10.
118. Novi F, Stanasila L, Giorgi F, Corsini GU, Cotecchia S, Maggio R. Paired activation of two components within muscarinic M3 receptor dimers is required for recruitment of beta-arrestin-1 to the plasma membrane. J Biol Chem 2005; 280: 19768-76.
119. Fiorentini C, Gardoni F, Spano P, Di Luca M, Missale C. Regulation of dopamine D1 receptor trafficking and desensitization by oligomerization with glutamate N-methyl-D-aspartate receptors. J Biol Chem 2003; 278: 20196-202.
120. Kim KM, Gainetdinov RR, Laporte SA, Caron MG, Barak LS. G protein-coupled receptor kinase regulates dopamine D3 receptor signaling by modulating the stability of a receptor-filamin-betaarrestin complex. A case of autoreceptor regulation. J Biol Chem 2005; 280: 12774-80.
121. Agnati LF, Fuxe K. Introductory remarks. J Mol Neurosci 2005; 26: 109-12.
122. Rashid AJ, So CH, Kong MM, et al. D1-D2 dopamine receptor heterooligomers with unique pharmacology are coupled to rapid activation of Gq/11 in the striatum. Proc Natl Acad Sci U S A 2007; 104: 654-9.
123. Daniels DJ, Kulkarni A, Xie Z, Bhushan RG, Portoghese PS. A bivalent ligand (KDAN-18) containing delta-antagonist and kappaagonist pharmacophores bridges delta2 and kappa1 opioid receptor phenotypes. J Med Chem 2005; 48: 1713-6.
124. Ferre S, Navarro G, Casado V, et al. G protein-coupled receptor heteromers as new targets for drug development. Prog Mol Biol Transl Sci 2010; 91: 41-52.
125. Marcellino D, Ferre S, Casado V, et al. Identification of dopamine D1-D3 receptor heteromers. Indications for a role of synergistic D1-D3 receptor interactions in the striatum. J Biol Chem 2008; 283: 26016-25.