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Extreme Vetting of Dopamine Receptor Oligomerization

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G-Protein-Coupled Receptor Dimers

Part of the book series: The Receptors ((REC,volume 33))

Abstract

Numerous reports have emerged over the past two decades suggesting that dopamine receptors form dimeric and/or higher-order oligomeric complexes. The existence of these complexes and their functional properties are of significant interest, as they may provide strategies for developing novel therapeutics that selectively target dopamine receptor complexes with the potential for more refined cellular therapeutics and reduced side-effects. However, there is still great debate and controversy surrounding the structural and functional aspects of dopamine receptor oligomers as well as their physiological relevance. Much of the uncertainty stems from the methodologies employed to understand these complexes, which have clear limitations and/or are not yet fully understood. Herein, we provide an overview of the literature focusing mainly on dopamine receptor homomeric complexes and selected dopamine receptor heteromeric complexes with the goal of providing a critical discussion of the methodology and the logic of the scientific inferences in this body of work.

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Abbreviations

GPCR:

G protein-coupled receptor

D1:

dopamine D1 receptor

D2:

dopamine D2 receptor

D3:

dopamine D3 receptor

D4:

dopamine D4 receptor

D5:

dopamine D5 receptor

mGlu5:

metabotropic glutamate receptor 5

NMDA:

N-methyl-D-aspartate receptors

GTP:

guanosine-5′-triphosphate

A2A:

adenosine A2A receptor

RET:

resonance energy transfer

FRET:

Förster resonance energy transfer

BRET:

bioluminescence resonance energy transfer

TR-FRET:

time-resolved resonance energy transfer

A:D:

acceptor-to-donor ratio

BiFC:

bimolecular fluorescence complementation

BiLC:

bimolecular luminescence complementation

CODA-RET:

complemented donor acceptor – resonance energy transfer

Rluc:

Renilla luciferase

EFRET :

FRET efficiency

FCS:

fluorescence correlation spectroscopy

PIE-FCCS:

pulsed-interleaved excitation fluorescence cross-correlation spectroscopy

FRAP:

fluorescence recovery after photobleaching

NLS:

nuclear localization sequence

TM:

transmembrane

IL:

intracellular loop

cAMP:

cyclic adenosine monophosphate

PLC:

phospholipase C

CaMKIIα:

calcium dependent protein kinase IIα

NAc:

nucleus accumbens

PLA:

proximity ligation assay

References

  1. Beaulieu JM, Gainetdinov RR. The physiology, signaling, and pharmacology of dopamine receptors. Pharmacol Rev. 2011;63(1):182–217.

    Article  CAS  PubMed  Google Scholar 

  2. Pei L, Lee FJ, Moszczynska A, Vukusic B, Liu F. Regulation of dopamine D1 receptor function by physical interaction with the NMDA receptors. J Neurosci. 2004;24(5):1149–58.

    Article  CAS  PubMed  Google Scholar 

  3. Kruse MS, Premont J, Krebs MO, Jay TM. Interaction of dopamine D1 with NMDA NR1 receptors in rat prefrontal cortex. Eur Neuropsychopharmacol. 2009;19(4):296–304.

    Article  CAS  PubMed  Google Scholar 

  4. Liu XY, Chu XP, Mao LM, Wang M, Lan HX, Li MH, et al. Modulation of D2R-NR2B interactions in response to cocaine. Neuron. 2006;52(5):897–909.

    Article  CAS  PubMed  Google Scholar 

  5. Navarro G, Moreno E, Aymerich M, Marcellino D, McCormick PJ, Mallol J, et al. Direct involvement of sigma-1 receptors in the dopamine D1 receptor-mediated effects of cocaine. Proc Natl Acad Sci U S A. 2010;107(43):18676–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Navarro G, Moreno E, Bonaventura J, Brugarolas M, Farre D, Aguinaga D, et al. Cocaine inhibits dopamine D2 receptor signaling via sigma-1-D2 receptor heteromers. PLoS One. 2013;8(4):e61245.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Lambert NA, Javitch JA. CrossTalk opposing view: weighing the evidence for class A GPCR dimers, the jury is still out. J Physiol. 2014;592(12):2443–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Frederick AL, Yano H, Trifilieff P, Vishwasrao HD, Biezonski D, Meszaros J, et al. Evidence against dopamine D1/D2 receptor heteromers. Mol Psychiatry. 2015;20(11):1373–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. O’Dowd BF, Ji X, Alijaniaram M, Rajaram RD, Kong MM, Rashid A, et al. Dopamine receptor oligomerization visualized in living cells. J Biol Chem. 2005;280(44):37225–35.

    Article  PubMed  CAS  Google Scholar 

  10. Herrick-Davis K, Grinde E, Cowan A, Mazurkiewicz JE. Fluorescence correlation spectroscopy analysis of serotonin, adrenergic, muscarinic, and dopamine receptor dimerization: the oligomer number puzzle. Mol Pharmacol. 2013;84(4):630–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Zawarynski P, Tallerico T, Seeman P, Lee SP, O’Dowd BF, George SR. Dopamine D2 receptor dimers in human and rat brain. FEBS Lett. 1998;441(3):383–6.

    Article  CAS  PubMed  Google Scholar 

  12. Armstrong D, Strange PG. Dopamine D2 receptor dimer formation: evidence from ligand binding. J Biol Chem. 2001;276(25):22621–9.

    Article  CAS  PubMed  Google Scholar 

  13. Wurch T, Matsumoto A, Pauwels PJ. Agonist-independent and -dependent oligomerization of dopamine D(2) receptors by fusion to fluorescent proteins. FEBS Lett 2001;507(1):109-13

    Google Scholar 

  14. Guo W, Shi L, Javitch JA. The fourth transmembrane segment forms the interface of the dopamine D2 receptor homodimer. J Biol Chem. 2003;278(7):4385–8.

    Article  CAS  PubMed  Google Scholar 

  15. Guo W, Shi L, Filizola M, Weinstein H, Javitch JA. Crosstalk in G protein-coupled receptors: changes at the transmembrane homodimer interface determine activation. Proc Natl Acad Sci U S A. 2005;102(48):17495–500.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Guo W, Urizar E, Kralikova M, Mobarec JC, Shi L, Filizola M, et al. Dopamine D2 receptors form higher order oligomers at physiological expression levels. EMBO J. 2008;27(17):2293–304.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. 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(9):688–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Albizu L, Cottet M, Kralikova M, Stoev S, Seyer R, Brabet I, et al. Time-resolved FRET between GPCR ligands reveals oligomers in native tissues. Nat Chem Biol. 2010;6(8):587–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Lane JR, Donthamsetti P, Shonberg J, Draper-Joyce CJ, Dentry S, Michino M, et al. A new mechanism of allostery in a G protein-coupled receptor dimer. Nat Chem Biol. 2014;10(9):745–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Nimchinsky EA, Hof PR, Janssen WG, Morrison JH, Schmauss C. Expression of dopamine D3 receptor dimers and tetramers in brain and in transfected cells. J Biol Chem. 1997;272(46):29229–37.

    Article  CAS  PubMed  Google Scholar 

  21. Pou C, Mannoury la Cour C, Stoddart LA, Millan MJ, Milligan G. Functional homomers and heteromers of dopamine D2L and D3 receptors co-exist at the cell surface. J Biol Chem. 2012;287(12):8864–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Marsango S, Caltabiano G, Pou C, Varela Liste MJ, Milligan G. Analysis of human dopamine D3 receptor quaternary structure. J Biol Chem. 2015;290(24):15146–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Van Craenenbroeck K, Borroto-Escuela DO, Romero-Fernandez W, Skieterska K, Rondou P, Lintermans B, et al. Dopamine D4 receptor oligomerization-contribution to receptor biogenesis. FEBS J. 2011;278(8):1333–44.

    Article  PubMed  CAS  Google Scholar 

  24. So CH, Varghese G, Curley KJ, Kong MMC, Alijaniaram M, Ji XD, et al. D1 and D2 dopamine receptors form heterooligomers and cointernalize after selective activation of either receptor. Mol Pharmacol. 2005;68(3):568–78.

    CAS  PubMed  Google Scholar 

  25. Dziedzicka-Wasylewska M, Faron-Gorecka A, Andrecka J, Polit A, Kusmider M, Wasylewski Z. Fluorescence studies reveal heterodimerization of dopamine D1 and D2 receptors in the plasma membrane. Biochemistry. 2006;45(29):8751–9.

    Article  CAS  PubMed  Google Scholar 

  26. Hasbi A, Fan T, Alijaniaram M, Nguyen T, Perreault ML, O’Dowd BF, et al. Calcium signaling cascade links dopamine D1-D2 receptor heteromer to striatal BDNF production and neuronal growth. Proc Natl Acad Sci U S A. 2009;106(50):21377–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. 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(1):59–69.

    Article  CAS  PubMed  Google Scholar 

  28. Marcellino D, Ferre S, Casado V, Cortes A, Le Foll B, Mazzola C, 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(38):26016–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Guitart X, Navarro G, Moreno E, Yano H, Cai NS, Sanchez-Soto M, et al. Functional selectivity of allosteric interactions within G protein-coupled receptor oligomers: the dopamine D1-D3 receptor heterotetramer. Mol Pharmacol 2014;86(4):417-29.

    Google Scholar 

  30. Hounsou C, Margathe JF, Oueslati N, Belhocine A, Dupuis E, Thomas C, et al. Time-resolved FRET binding assay to investigate hetero-oligomer binding properties: proof of concept with dopamine D1/D3 heterodimer. ACS Chem Biol. 2015;10(2):466–74.

    Article  CAS  PubMed  Google Scholar 

  31. So CH, Verma V, Alijaniaram M, Cheng R, Rashid AJ, O’Dowd BF, et al. Calcium signaling by dopamine D5 receptor and D5-D2 receptor hetero-oligomers occurs by a mechanism distinct from that for dopamine D1-D2 receptor hetero-oligomers. Mol Pharmacol. 2009;75(4):843–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. O’Dowd BF, Nguyen T, Ji X, George SR. D5 dopamine receptor carboxyl tail involved in D5-D2 heteromer formation. Biochem Biophys Res Commun. 2013;431(3):586–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Borroto-Escuela DO, Van Craenenbroeck K, Romero-Fernandez W, Guidolin D, Woods AS, Rivera A, et al. Dopamine D2 and D4 receptor heteromerization and its allosteric receptor-receptor interactions. Biochem Biophys Res Commun. 2011;404(4):928–34.

    Article  CAS  PubMed  Google Scholar 

  34. Scarselli M, Novi F, Schallmach E, Lin R, Baragli A, Colzi A, et al. D2/D3 dopamine receptor heterodimers exhibit unique functional properties. J Biol Chem. 2001;276(32):30308–14.

    Article  CAS  PubMed  Google Scholar 

  35. Gildea JJ, Shah IT, Van Sciver RE, Israel JA, Enzensperger C, McGrath HE, et al. The cooperative roles of the dopamine receptors, D1R and D5R, on the regulation of renal sodium transport. Kidney Int. 2014;86(1):118–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Rashid AJ, So CH, Kong MM, Furtak T, El-Ghundi M, Cheng R, 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(2):654–9.

    Article  CAS  PubMed  Google Scholar 

  37. Perreault ML, Fan T, O’Dowd BF, George SR. Enhanced brain-derived neurotrophic factor signaling in the nucleus accumbens of juvenile rats. Dev Neurosci. 2013;35(5):384–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Pei L, Li S, Wang M, Diwan M, Anisman H, Fletcher PJ, et al. Uncoupling the dopamine D1-D2 receptor complex exerts antidepressant-like effects. Nat Med. 2010;16(12):1393–5.

    Article  CAS  PubMed  Google Scholar 

  39. Gines S, Hillion J, Torvinen M, Le Crom S, Casado V, Canela EI, et al. Dopamine D1 and adenosine A1 receptors form functionally interacting heteromeric complexes. Proc Natl Acad Sci U S A. 2000;97(15):8606–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Toda S, Alguacil LF, Kalivas PW. Repeated cocaine administration changes the function and subcellular distribution of adenosine A1 receptor in the rat nucleus accumbens. J Neurochem. 2003;87(6):1478–84.

    Article  CAS  PubMed  Google Scholar 

  41. Hillion J, Canals M, Torvinen M, Casado V, Scott R, Terasmaa A, et al. Coaggregation, cointernalization, and codesensitization of adenosine A2A receptors and dopamine D2 receptors. J Biol Chem. 2002;277(20):18091–7.

    Article  CAS  PubMed  Google Scholar 

  42. Ciruela F, Burgueno J, Casado V, Canals M, Marcellino D, Goldberg SR, et al. Combining mass spectrometry and pull-down techniques for the study of receptor heteromerization. Direct epitope-epitope electrostatic interactions between adenosine A2A and dopamine D2 receptors. Anal Chem. 2004;76(18):5354–63.

    Article  CAS  PubMed  Google Scholar 

  43. Trifilieff P, Rives ML, Urizar E, Piskorowski RA, Vishwasrao HD, Castrillon J, et al. Detection of antigen interactions ex vivo by proximity ligation assay: endogenous dopamine D2-adenosine A2A receptor complexes in the striatum. BioTechniques. 2011;51(2):111–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Torvinen M, Marcellino D, Canals M, Agnati LF, Lluis C, Franco R, et al. Adenosine A2A receptor and dopamine D3 receptor interactions: evidence of functional A2A/D3 heteromeric complexes. Mol Pharmacol. 2005;67(2):400–7.

    Article  CAS  PubMed  Google Scholar 

  45. Li H, Zhang Z, Blackburn MR, Wang SW, Ribelayga CP, O’Brien J. Adenosine and dopamine receptors coregulate photoreceptor coupling via gap junction phosphorylation in mouse retina. J Neurosci. 2013;33(7):3135–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Cabello N, Gandia J, Bertarelli DC, Watanabe M, Lluis C, Franco R, et al. Metabotropic glutamate type 5, dopamine D2 and adenosine A2a receptors form higher-order oligomers in living cells. J Neurochem. 2009;109(5):1497–507.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Carriba P, Navarro G, Ciruela F, Ferre S, Casado V, Agnati L, et al. Detection of heteromerization of more than two proteins by sequential BRET-FRET. Nat Methods. 2008;5(8):727–33.

    Article  CAS  PubMed  Google Scholar 

  48. Gonzalez S, Moreno-Delgado D, Moreno E, Perez-Capote K, Franco R, Mallol J, et al. Circadian-related heteromerization of adrenergic and dopamine D(4) receptors modulates melatonin synthesis and release in the pineal gland. PLoS Biol. 2012;10(6):e1001347.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Rebois RV, Maki K, Meeks JA, Fishman PH, Hebert TE, Northup JK. D2-like dopamine and beta-adrenergic receptors form a signaling complex that integrates Gs- and Gi-mediated regulation of adenylyl cyclase. Cell Signal. 2012;24(11):2051–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Zeng C, Luo Y, Asico LD, Hopfer U, Eisner GM, Felder RA, et al. Perturbation of D1 dopamine and AT1 receptor interaction in spontaneously hypertensive rats. Hypertension. 2003;42(4):787–92.

    Article  CAS  PubMed  Google Scholar 

  51. Martinez-Pinilla E, Rodriguez-Perez AI, Navarro G, Aguinaga D, Moreno E, Lanciego JL, et al. Dopamine D2 and angiotensin II type 1 receptors form functional heteromers in rat striatum. Biochem Pharmacol. 2015;96(2):131–42.

    Article  CAS  PubMed  Google Scholar 

  52. Zeng C, Asico LD, Wang X, Hopfer U, Eisner GM, Felder RA, et al. Angiotensin II regulation of AT1 and D3 dopamine receptors in renal proximal tubule cells of SHR. Hypertension. 2003;41(3 Pt 2):724–9.

    Article  CAS  PubMed  Google Scholar 

  53. Zeng C, Yang Z, Wang Z, Jones J, Wang X, Altea J, et al. Interaction of angiotensin II type 1 and D5 dopamine receptors in renal proximal tubule cells. Hypertension. 2005;45(4):804–10.

    Article  CAS  PubMed  Google Scholar 

  54. Marcellino D, Carriba P, Filip M, Borgkvist A, Frankowska M, Bellido I, et al. Antagonistic cannabinoid CB1/dopamine D2 receptor interactions in striatal CB1/D2 heteromers. A combined neurochemical and behavioral analysis. Neuropharmacology. 2008;54(5):815–23.

    Article  CAS  PubMed  Google Scholar 

  55. Khan SS, Lee FJ. Delineation of domains within the cannabinoid CB1 and dopamine D2 receptors that mediate the formation of the heterodimer complex. J Mol Neurosci. 2014;53(1):10–21.

    Article  CAS  PubMed  Google Scholar 

  56. Navarro G, Carriba P, Gandia J, Ciruela F, Casado V, Cortes A, et al. 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. ScientificWorldJournal. 2008;8:1088–97.

    Article  CAS  PubMed  Google Scholar 

  57. Bonaventura J, Rico AJ, Moreno E, Sierra S, Sanchez M, Luquin N, et al. L-DOPA-treatment in primates disrupts the expression of A(2A) adenosine-CB(1) cannabinoid-D(2) dopamine receptor heteromers in the caudate nucleus. Neuropharmacology. 2014;79:90–100.

    Article  CAS  PubMed  Google Scholar 

  58. Dasgupta S, Li XM, Jansson A, Finnman UB, Matsui T, Rinken A, et al. Regulation of dopamine D2 receptor affinity by cholecystokinin octapeptide in fibroblast cells cotransfected with human CCKB and D2L receptor cDNAs. Brain Res Mol Brain Res. 1996;36(2):292–9.

    Article  CAS  PubMed  Google Scholar 

  59. Borroto-Escuela DO, Romero-Fernandez W, Garriga P, Ciruela F, Narvaez M, Tarakanov AO, et al. G protein-coupled receptor heterodimerization in the brain. Methods Enzymol. 2013;521:281–94.

    Article  CAS  PubMed  Google Scholar 

  60. Fuenzalida J, Galaz P, Araya KA, Slater PG, Blanco EH, Campusano JM, et al. Dopamine D1 and corticotrophin-releasing hormone type-2alpha receptors assemble into functionally interacting complexes in living cells. Br J Pharmacol. 2014;171(24):5650–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Zeng C, Asico LD, Yu C, Villar VA, Shi W, Luo Y, et al. Renal D3 dopamine receptor stimulation induces natriuresis by endothelin B receptor interactions. Kidney Int. 2008;74(6):750–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Yu C, Yang Z, Ren H, Zhang Y, Han Y, He D, et al. D3 dopamine receptor regulation of ETB receptors in renal proximal tubule cells from WKY and SHRs. Am J Hypertens. 2009;22(8):877–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Moreno E, Vaz SH, Cai NS, Ferrada C, Quiroz C, Barodia SK, et al. Dopamine-galanin receptor heteromers modulate cholinergic neurotransmission in the rat ventral hippocampus. J Neurosci. 2011;31(20):7412–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Jiang H, Betancourt L, Smith RG. Ghrelin amplifies dopamine signaling by cross talk involving formation of growth hormone secretagogue receptor/dopamine receptor subtype 1 heterodimers. Mol Endocrinol. 2006;20(8):1772–85.

    Article  CAS  PubMed  Google Scholar 

  65. Schellekens H, van Oeffelen WE, Dinan TG, Cryan JF. Promiscuous dimerization of the growth hormone secretagogue receptor (GHS-R1a) attenuates ghrelin-mediated signaling. J Biol Chem. 2013;288(1):181–91.

    Article  CAS  PubMed  Google Scholar 

  66. Kern A, Albarran-Zeckler R, Walsh HE, Smith RG. Apo-ghrelin receptor forms heteromers with DRD2 in hypothalamic neurons and is essential for anorexigenic effects of DRD2 agonism. Neuron. 2012;73(2):317–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Ferrada C, Moreno E, Casado V, Bongers G, Cortes A, Mallol J, et al. Marked changes in signal transduction upon heteromerization of dopamine D1 and histamine H3 receptors. Br J Pharmacol. 2009;157(1):64–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Moreno E, Hoffmann H, Gonzalez-Sepulveda M, Navarro G, Casado V, Cortes A, et al. Dopamine D1-histamine H3 receptor heteromers provide a selective link to MAPK signaling in GABAergic neurons of the direct striatal pathway. J Biol Chem. 2011;286(7):5846–54.

    Article  CAS  PubMed  Google Scholar 

  69. Ferrada C, Ferre S, Casado V, Cortes A, Justinova Z, Barnes C, et al. Interactions between histamine H3 and dopamine D2 receptors and the implications for striatal function. Neuropharmacology. 2008;55(2):190–7.

    Article  CAS  PubMed  Google Scholar 

  70. Moreno E, Moreno-Delgado D, Navarro G, Hoffmann HM, Fuentes S, Rosell-Vilar S, et al. Cocaine disrupts histamine H3 receptor modulation of dopamine D1 receptor signaling: sigma1-D1-H3 receptor complexes as key targets for reducing cocaine’s effects. J Neurosci. 2014;34(10):3545–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Koschatzky S, Tschammer N, Gmeiner P. Cross-receptor interactions between dopamine D2L and neurotensin NTS1 receptors modulate binding affinities of dopaminergics. ACS Chem Neurosci. 2011;2(6):308–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Borroto-Escuela DO, Ravani A, Tarakanov AO, Brito I, Narvaez M, Romero-Fernandez W, et al. Dopamine D2 receptor signaling dynamics of dopamine D2-neurotensin 1 receptor heteromers. Biochem Biophys Res Commun. 2013;435(1):140–6.

    Article  CAS  PubMed  Google Scholar 

  73. Koschatzky S, Gmeiner P. Selective agonists for dopamine/neurotensin receptor heterodimers. ChemMedChem. 2012;7(3):509–14.

    Article  CAS  PubMed  Google Scholar 

  74. Juhasz JR, Hasbi A, Rashid AJ, So CH, George SR, O’Dowd BF. Mu-opioid receptor heterooligomer formation with the dopamine D1 receptor as directly visualized in living cells. Eur J Pharmacol. 2008;581(3):235–43.

    Article  CAS  PubMed  Google Scholar 

  75. Suarez-Boomgaard D, Gago B, Valderrama-Carvajal A, Roales-Bujan R, Van Craenenbroeck K, Duchou J, et al. Dopamine D(4) receptor counteracts morphine-induced changes in micro opioid receptor signaling in the striosomes of the rat caudate putamen. Int J Mol Sci. 2014;15(1):1481–98.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  76. Romero-Fernandez W, Borroto-Escuela DO, Agnati LF, Fuxe K. Evidence for the existence of dopamine D2-oxytocin receptor heteromers in the ventral and dorsal striatum with facilitatory receptor-receptor interactions. Mol Psychiatry. 2013;18(8):849–50.

    Article  CAS  PubMed  Google Scholar 

  77. Dunham JH, Meyer RC, Garcia EL, Hall RA. GPR37 surface expression enhancement via N-terminal truncation or protein-protein interactions. Biochemistry. 2009;48(43):10286–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Lukasiewicz S, Polit A, Kedracka-Krok S, Wedzony K, Mackowiak M, Dziedzicka-Wasylewska M. Hetero-dimerization of serotonin 5-HT(2A) and dopamine D(2) receptors. Biochim Biophys Acta. 2010;1803(12):1347–58.

    Article  CAS  PubMed  Google Scholar 

  79. Borroto-Escuela DO, Romero-Fernandez W, Tarakanov AO, Marcellino D, Ciruela F, Agnati LF, et al. Dopamine D2 and 5-hydroxytryptamine 5-HT((2)A) receptors assemble into functionally interacting heteromers. Biochem Biophys Res Commun. 2010;401(4):605–10.

    Article  CAS  PubMed  Google Scholar 

  80. Lukasiewicz S, Faron-Gorecka A, Kedracka-Krok S, Dziedzicka-Wasylewska M. Effect of clozapine on the dimerization of serotonin 5-HT(2A) receptor and its genetic variant 5-HT(2A)H425Y with dopamine D(2) receptor. Eur J Pharmacol. 2011;659(2-3):114–23.

    Article  CAS  PubMed  Google Scholar 

  81. Albizu L, Holloway T, Gonzalez-Maeso J, Sealfon SC. Functional crosstalk and heteromerization of serotonin 5-HT2A and dopamine D2 receptors. Neuropharmacology. 2011;61(4):770–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Borroto-Escuela DO, Romero-Fernandez W, Narvaez M, Oflijan J, Agnati LF, Fuxe K. Hallucinogenic 5-HT2AR agonists LSD and DOI enhance dopamine D2R protomer recognition and signaling of D2-5-HT2A heteroreceptor complexes. Biochem Biophys Res Commun. 2014;443(1):278–84.

    Article  CAS  PubMed  Google Scholar 

  83. Baragli A, Alturaihi H, Watt HL, Abdallah A, Kumar U. Heterooligomerization of human dopamine receptor 2 and somatostatin receptor 2 Co-immunoprecipitation and fluorescence resonance energy transfer analysis. Cell Signal. 2007;19(11):2304–16.

    Article  CAS  PubMed  Google Scholar 

  84. Rocheville M, Lange DC, Kumar U, Patel SC, Patel RC, Patel YC. Receptors for dopamine and somatostatin: formation of hetero-oligomers with enhanced functional activity. Science. 2000;288(5463):154–7.

    Article  CAS  PubMed  Google Scholar 

  85. Szafran K, Lukasiewicz S, Faron-Gorecka A, Kolasa M, Kusmider M, Solich J, et al. Antidepressant drugs promote the heterodimerization of the dopamine D2 and somatostatin Sst5 receptors–fluorescence in vitro studies. Pharmacol Rep. 2012;64(5):1253–8.

    Article  CAS  PubMed  Google Scholar 

  86. Espinoza S, Salahpour A, Masri B, Sotnikova TD, Messa M, Barak LS, et al. Functional interaction between trace amine-associated receptor 1 and dopamine D2 receptor. Mol Pharmacol. 2011;80(3):416–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Bouvier C, Potier M, Beauregard G, Lafond J, Amlaiky N, Caron MG, et al. Solubilization and characterization of D2-dopamine receptors in an estrone-induced, prolactin-secreting rat pituitary adenoma. J Neurochem. 1986;47(5):1653–60.

    Article  CAS  PubMed  Google Scholar 

  88. Bouvier C, Lagace G, Potier M, Collu R. Structural differences between dopamine D2 receptors present in a rat pituitary adenoma and in transplantable rat pituitary tumors 7315a and MtTW15. J Neurochem. 1990;54(3):815–22.

    Article  CAS  PubMed  Google Scholar 

  89. Seeman P, Guan HC, Civelli O, Van Tol HH, Sunahara RK, Niznik HB. The cloned dopamine D2 receptor reveals different densities for dopamine receptor antagonist ligands. Implications for human brain positron emission tomography. Eur J Pharmacol. 1992;227(2):139–46.

    Article  CAS  PubMed  Google Scholar 

  90. Ng GY, O’Dowd BF, Lee SP, Chung HT, Brann MR, Seeman P, et al. Dopamine D2 receptor dimers and receptor-blocking peptides. Biochem Biophys Res Commun. 1996;227(1):200–4.

    Article  CAS  PubMed  Google Scholar 

  91. Obregon F, Urbina M, Lima L. [3H]raclopride and [3H]spiroperidol binding to retinal membranes of the teleost Eugerres plumieri: effect of light and dark adaptation. Neurochem Int. 1997;31(4):541–8.

    Article  CAS  PubMed  Google Scholar 

  92. Malmberg A, Jerning E, Mohell N. Critical reevaluation of spiperone and benzamide binding to dopamine D2 receptors: evidence for identical binding sites. Eur J Pharmacol. 1996;303(1-2):123–8.

    Article  CAS  PubMed  Google Scholar 

  93. Chabre M, Deterre P, Antonny B. The apparent cooperativity of some GPCRs does not necessarily imply dimerization. Trends Pharmacol Sci. 2009;30(4):182–7.

    Article  CAS  PubMed  Google Scholar 

  94. Strange PG. Oligomers of D2 dopamine receptors: evidence from ligand binding. J Mol Neurosci. 2005;26(2-3):155–60.

    Article  CAS  PubMed  Google Scholar 

  95. Ng GY, Mouillac B, George SR, Caron M, Dennis M, Bouvier M, et al. Desensitization, phosphorylation and palmitoylation of the human dopamine D1 receptor. Eur J Pharmacol. 1994;267(1):7–19.

    Article  CAS  PubMed  Google Scholar 

  96. Ng GY, O’Dowd BF, Caron M, Dennis M, Brann MR, George SR. Phosphorylation and palmitoylation of the human D2L dopamine receptor in Sf9 cells. J Neurochem. 1994;63(5):1589–95.

    Article  CAS  PubMed  Google Scholar 

  97. George SR, Lee SP, Varghese G, Zeman PR, Seeman P, Ng GY, et al. A transmembrane domain-derived peptide inhibits D1 dopamine receptor function without affecting receptor oligomerization. J Biol Chem. 1998;273(46):30244–8.

    Article  CAS  PubMed  Google Scholar 

  98. Lee SP, So CH, Rashid AJ, Varghese G, Cheng R, Lanca AJ, et al. Dopamine D1 and D2 receptor co-activation generates a novel phospholipase C-mediated calcium signal. J Biol Chem. 2004;279(34):35671–8.

    Article  CAS  PubMed  Google Scholar 

  99. Gazi L, Lopez-Gimenez JF, Rudiger MP, Strange PG. Constitutive oligomerization of human D2 dopamine receptors expressed in Spodoptera frugiperda 9 (Sf9) and in HEK293 cells. Analysis using co-immunoprecipitation and time-resolved fluorescence resonance energy transfer. Eur J Biochem. 2003;270(19):3928–38.

    Article  CAS  PubMed  Google Scholar 

  100. Kawano K, Yano Y, Omae K, Matsuzaki S, Matsuzaki K. Stoichiometric analysis of oligomerization of membrane proteins on living cells using coiled-coil labeling and spectral imaging. Anal Chem. 2013;85(6):3454–61.

    Article  CAS  PubMed  Google Scholar 

  101. James JR, Oliveira MI, Carmo AM, Iaboni A, Davis SJ. A rigorous experimental framework for detecting protein oligomerization using bioluminescence resonance energy transfer. Nat Methods. 2006;3(12):1001–6.

    Article  CAS  PubMed  Google Scholar 

  102. Kenworthy AK. Imaging protein-protein interactions using fluorescence resonance energy transfer microscopy. Methods. 2001;24(3):289–96.

    Article  CAS  PubMed  Google Scholar 

  103. Szalai B, Hoffmann P, Prokop S, Erdelyi L, Varnai P, Hunyady L. Improved methodical approach for quantitative BRET analysis of G Protein Coupled Receptor dimerization. PLoS One. 2014;9(10):e109503.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  104. Lan TH, Liu Q, Li C, Wu G, Steyaert J, Lambert NA. BRET evidence that beta2 adrenergic receptors do not oligomerize in cells. Sci Rep. 2015;5:10166.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Kong MM, Fan T, Varghese G, O’Dowd BF, George SR. Agonist-induced cell surface trafficking of an intracellularly sequestered D1 dopamine receptor homo-oligomer. Mol Pharmacol. 2006;70(1):78–89.

    CAS  PubMed  Google Scholar 

  106. Lan TH, Wu G, Lambert NA. Lateral diffusion contributes to FRET from lanthanide-tagged membrane proteins. Biochem Biophys Res Commun. 2015;464(1):244–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Vidi PA, Chemel BR, Hu CD, Watts VJ. Ligand-dependent oligomerization of dopamine D(2) and adenosine A(2A) receptors in living neuronal cells. Mol Pharmacol. 2008;74(3):544–51.

    Article  CAS  PubMed  Google Scholar 

  108. Hu CD, Chinenov Y, Kerppola TK. Visualization of interactions among bZIP and Rel family proteins in living cells using bimolecular fluorescence complementation. Mol Cell. 2002;9(4):789–98.

    Article  CAS  PubMed  Google Scholar 

  109. Vidi P-A, Ejendal KFK, Przybyla JA, Watts VJ. Fluorescent protein complementation assays: new tools to study G protein-coupled receptor oligomerization and GPCR-mediated signaling. Mol Cell Endocrinol. 2011;331(2):185–93.

    Article  CAS  PubMed  Google Scholar 

  110. Rebois RV, Robitaille M, Petrin D, Zylbergold P, Trieu P, Hebert TE. Combining protein complementation assays with resonance energy transfer to detect multipartner protein complexes in living cells. Methods. 2008;45(3):214–8.

    Article  CAS  PubMed  Google Scholar 

  111. Urizar E, Yano H, Kolster R, Gales C, Lambert N, Javitch JA. CODA-RET reveals functional selectivity as a result of GPCR heteromerization. Nat Chem Biol. 2011;7(9):624–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Niswender CM, Jones CK, Lin X, Bubser M, Thompson Gray A, Blobaum AL, et al. Development and antiparkinsonian activity of VU0418506, a selective positive allosteric modulator of metabotropic glutamate receptor 4 homomers without activity at mGlu2/4 heteromers. ACS Chem Neurosci. 2016;7(9):1201–11.

    Article  CAS  PubMed  Google Scholar 

  113. Perreault ML, Hasbi A, Alijaniaram M, Fan T, Varghese G, Fletcher PJ, et al. The dopamine D1-D2 receptor heteromer localizes in dynorphin/enkephalin neurons: increased high affinity state following amphetamine and in schizophrenia. J Biol Chem. 2010;285(47):36625–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Piston DW, Kremers GJ. Fluorescent protein FRET: the good, the bad and the ugly. Trends Biochem Sci. 2007;32(9):407–14.

    Article  CAS  PubMed  Google Scholar 

  115. Periasamy A, Wallrabe H, Chen Y, Barroso M. Chapter 22: Quantitation of protein-protein interactions: confocal FRET microscopy. Methods Cell Biol. 2008;89:569–98.

    Article  CAS  PubMed  Google Scholar 

  116. Enderlein J, Gregor I, Patra D, Fitter J. Art and artefacts of fluorescence correlation spectroscopy. Curr Pharm Biotechnol. 2004;5(2):155–61.

    Article  CAS  PubMed  Google Scholar 

  117. Smith AW. Detection of rhodopsin dimerization in situ by PIE-FCCS, a time-resolved fluorescence spectroscopy. Methods Mol Biol. 2015;1271:205–19.

    Article  CAS  PubMed  Google Scholar 

  118. Dorsch S, Klotz KN, Engelhardt S, Lohse MJ, Bunemann M. Analysis of receptor oligomerization by FRAP microscopy. Nat Methods. 2009;6(3):225–30.

    Article  CAS  PubMed  Google Scholar 

  119. Fonseca JM, Lambert NA. Instability of a class a G protein-coupled receptor oligomer interface. Mol Pharmacol. 2009;75(6):1296–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Tabor A, Weisenburger S, Banerjee A, Purkayastha N, Kaindl JM, Hubner H, et al. Visualization and ligand-induced modulation of dopamine receptor dimerization at the single molecule level. Sci Rep. 2016;6:33233.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Zheng Q, Juette MF, Jockusch S, Wasserman MR, Zhou Z, Altman RB, et al. Ultra-stable organic fluorophores for single-molecule research. Chem Soc Rev. 2014;43(4):1044–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Hern JA, Baig AH, Mashanov GI, Birdsall B, Corrie JE, Lazareno S, et al. Formation and dissociation of M1 muscarinic receptor dimers seen by total internal reflection fluorescence imaging of single molecules. Proc Natl Acad Sci U S A. 2010;107(6):2693–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Juette MF, Terry DS, Wasserman MR, Zhou Z, Altman RB, Zheng Q, et al. The bright future of single-molecule fluorescence imaging. Curr Opin Chem Biol. 2014;20:103–11.

    Article  CAS  PubMed  Google Scholar 

  124. Lee SP, O’Dowd BF, Ng GY, Varghese G, Akil H, Mansour A, et al. Inhibition of cell surface expression by mutant receptors demonstrates that D2 dopamine receptors exist as oligomers in the cell. Mol Pharmacol. 2000;58(1):120–8.

    CAS  PubMed  Google Scholar 

  125. Karpa KD, Lin R, Kabbani N, Levenson R. The dopamine D3 receptor interacts with itself and the truncated D3 splice variant d3nf: D3-D3nf interaction causes mislocalization of D3 receptors. Mol Pharmacol. 2000;58(4):677–83.

    CAS  PubMed  Google Scholar 

  126. Elmhurst JL, Xie Z, O’Dowd BF, George SR. The splice variant D3nf reduces ligand binding to the D3 dopamine receptor: evidence for heterooligomerization. Brain Res Mol Brain Res. 2000;80(1):63–74.

    Article  CAS  PubMed  Google Scholar 

  127. O’Dowd BF, Ji X, Alijaniaram M, Nguyen T, George SR. Separation and reformation of cell surface dopamine receptor oligomers visualized in cells. Eur J Pharmacol. 2011;658(2-3):74–83.

    Article  PubMed  CAS  Google Scholar 

  128. Calebiro D, Rieken F, Wagner J, Sungkaworn T, Zabel U, Borzi A, et al. Single-molecule analysis of fluorescently labeled G-protein-coupled receptors reveals complexes with distinct dynamics and organization. Proc Natl Acad Sci U S A. 2013;110(2):743–8.

    Article  CAS  PubMed  Google Scholar 

  129. Hebert TE, Moffett S, Morello JP, Loisel TP, Bichet DG, Barret C, et al. A peptide derived from a beta2-adrenergic receptor transmembrane domain inhibits both receptor dimerization and activation. J Biol Chem. 1996;271(27):16384–92.

    Article  CAS  PubMed  Google Scholar 

  130. Lee SP, O’Dowd BF, Rajaram RD, Nguyen T, George SR. D2 dopamine receptor homodimerization is mediated by multiple sites of interaction, including an intermolecular interaction involving transmembrane domain 4. Biochemistry. 2003;42(37):11023–31.

    Article  CAS  PubMed  Google Scholar 

  131. Canals M, Marcellino D, Fanelli F, Ciruela F, de Benedetti P, Goldberg SR, et al. Adenosine A2A-dopamine D2 receptor-receptor heteromerization: qualitative and quantitative assessment by fluorescence and bioluminescence energy transfer. J Biol Chem. 2003;278(47):46741–9.

    Article  CAS  PubMed  Google Scholar 

  132. O’Dowd BF, Ji X, Nguyen T, George SR. Two amino acids in each of D1 and D2 dopamine receptor cytoplasmic regions are involved in D1-D2 heteromer formation. Biochem Biophys Res Commun. 2012;417(1):23–8.

    Article  PubMed  CAS  Google Scholar 

  133. Borroto-Escuela DO, Marcellino D, Narvaez M, Flajolet M, Heintz N, Agnati L, et al. A serine point mutation in the adenosine A2AR C-terminal tail reduces receptor heteromerization and allosteric modulation of the dopamine D2R. Biochem Biophys Res Commun. 2010;394(1):222–7.

    Article  CAS  PubMed  Google Scholar 

  134. Perreault ML, Hasbi A, O’Dowd BF, George SR. Heteromeric dopamine receptor signaling complexes: emerging neurobiology and disease relevance. Neuropsychopharmacology. 2014;39(1):156–68.

    Article  CAS  PubMed  Google Scholar 

  135. Nygaard R, Zou Y, Dror RO, Mildorf TJ, Arlow DH, Manglik A, et al. The dynamic process of beta(2)-adrenergic receptor activation. Cell. 2013;152(3):532–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Manglik A, Kim TH, Masureel M, Altenbach C, Yang Z, Hilger D, et al. Structural insights into the dynamic process of beta2-adrenergic receptor signaling. Cell. 2015;161(5):1101–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Sounier R, Mas C, Steyaert J, Laeremans T, Manglik A, Huang W, et al. Propagation of conformational changes during mu-opioid receptor activation. Nature. 2015;524(7565):375–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Lamichhane R, Liu JJ, Pljevaljcic G, White KL, van der Schans E, Katritch V, et al. Single-molecule view of basal activity and activation mechanisms of the G protein-coupled receptor beta2AR. Proc Natl Acad Sci U S A. 2015;112(46):14254–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. George SR, Kern A, Smith RG, Franco R. Dopamine receptor heteromeric complexes and their emerging functions. Prog Brain Res. 2014;211:183–200.

    Article  CAS  PubMed  Google Scholar 

  140. Lee S-M, Kant A, Blake D, Murthy V, Boyd K, Wyrick SJ, et al. SKF-83959 is not a highly-biased functionally selective D1 dopamine receptor ligand with activity at phospholipase C. Neuropharmacology. 2014;86:145–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Chun LS, Free RB, Doyle TB, Huang XP, Rankin ML, Sibley DR. D1-D2 dopamine receptor synergy promotes calcium signaling via multiple mechanisms. Mol Pharmacol. 2013;84(2):190–200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Gerfen CR. The neostriatal mosaic: multiple levels of compartmental organization. Trends Neurosci. 1992;15(4):133–9.

    Article  CAS  PubMed  Google Scholar 

  143. Hersch SM, Ciliax BJ, Gutekunst CA, Rees HD, Heilman CJ, Yung KK, et al. Electron microscopic analysis of D1 and D2 dopamine receptor proteins in the dorsal striatum and their synaptic relationships with motor corticostriatal afferents. J Neurosci. 1995;15(7 Pt 2):5222–37.

    CAS  PubMed  Google Scholar 

  144. Le Moine C, Bloch B. D1 and D2 dopamine receptor gene expression in the rat striatum: sensitive cRNA probes demonstrate prominent segregation of D1 and D2 mRNAs in distinct neuronal populations of the dorsal and ventral striatum. J Comp Neurol. 1995;355(3):418–26.

    Article  PubMed  Google Scholar 

  145. Perreault ML, Hasbi A, O’Dowd BF, George SR. The dopamine D1–D2 receptor heteromer in striatal medium spiny neurons: evidence for a third distinct neuronal pathway in Basal Ganglia. Front Neuroanat. 2011;5:31.

    Article  PubMed  PubMed Central  Google Scholar 

  146. Gagnon D, Petryszyn S, Sanchez MG, Bories C, Beaulieu JM, De Koninck Y, et al. Striatal neurons expressing D1 and D2 receptors are morphologically distinct and differently affected by dopamine denervation in mice. Sci Rep. 2017;7:41432.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Biezonski DK, Trifilieff P, Meszaros J, Javitch JA, Kellendonk C. Evidence for limited D1 and D2 receptor coexpression and colocalization within the dorsal striatum of the neonatal mouse. J Comp Neurol. 2015;523(8):1175–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Fuxe K, Ungerstedt U. Action of caffeine and theophyllamine on supersensitive dopamine receptors: considerable enhancement of receptor response to treatment with DOPA and dopamine receptor agonists. Med Biol. 1974;52(1):48–54.

    CAS  PubMed  Google Scholar 

  149. Ferre S, Fuxe K, von Euler G, Johansson B, Fredholm BB. Adenosine-dopamine interactions in the brain. Neuroscience. 1992;51(3):501–12.

    Article  CAS  PubMed  Google Scholar 

  150. Snyder SH, Katims JJ, Annau Z, Bruns RF, Daly JW. Adenosine receptors and behavioral actions of methylxanthines. Proc Natl Acad Sci U S A. 1981;78(5):3260–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Ferre S, von Euler G, Johansson B, Fredholm BB, Fuxe K. Stimulation of high-affinity adenosine A2 receptors decreases the affinity of dopamine D2 receptors in rat striatal membranes. Proc Natl Acad Sci U S A. 1991;88(16):7238–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Ferre S, Agnati LF, Ciruela F, Lluis C, Woods AS, Fuxe K, et al. Neurotransmitter receptor heteromers and their integrative role in ‘local modules’: the striatal spine module. Brain Res Rev. 2007;55(1):55–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Franco R, Lluis C, Canela EI, Mallol J, Agnati L, Casado V, et al. Receptor-receptor interactions involving adenosine A1 or dopamine D1 receptors and accessory proteins. J Neural Transm (Vienna). 2007;114(1):93–104.

    Article  CAS  Google Scholar 

  154. Fuxe K, Marcellino D, Rivera A, Diaz-Cabiale Z, Filip M, Gago B, et al. Receptor-receptor interactions within receptor mosaics. Impact on neuropsychopharmacology. Brain Res Rev. 2008;58(2):415–52.

    Article  CAS  PubMed  Google Scholar 

  155. Azdad K, Gall D, Woods AS, Ledent C, Ferre S, Schiffmann SN. Dopamine D2 and adenosine A2A receptors regulate NMDA-mediated excitation in accumbens neurons through A2A-D2 receptor heteromerization. Neuropsychopharmacology. 2009;34(4):972–86.

    Article  CAS  PubMed  Google Scholar 

  156. Grondin R, Bedard PJ, Hadj Tahar A, Gregoire L, Mori A, Kase H. Antiparkinsonian effect of a new selective adenosine A2A receptor antagonist in MPTP-treated monkeys. Neurology. 1999;52(8):1673–7.

    Article  CAS  PubMed  Google Scholar 

  157. Ikeda K, Kurokawa M, Aoyama S, Kuwana Y. Neuroprotection by adenosine A2A receptor blockade in experimental models of Parkinson’s disease. J Neurochem. 2002;80(2):262–70.

    Article  CAS  PubMed  Google Scholar 

  158. Schwarzschild MA, Xu K, Oztas E, Petzer JP, Castagnoli K, Castagnoli N Jr, et al. Neuroprotection by caffeine and more specific A2A receptor antagonists in animal models of Parkinson’s disease. Neurology. 2003;61(11 Suppl 6):S55–61.

    Article  CAS  PubMed  Google Scholar 

  159. Hanson SM, Gurevich EV, Vishnivetskiy SA, Ahmed MR, Song X, Gurevich VV. Each rhodopsin molecule binds its own arrestin. Proc Natl Acad Sci U S A. 2007;104(9):3125–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Whorton MR, Bokoch MP, Rasmussen SG, Huang B, Zare RN, Kobilka B, 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(18):7682–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Whorton MR, Jastrzebska B, Park PS, Fotiadis D, Engel A, Palczewski K, et al. Efficient coupling of transducin to monomeric rhodopsin in a phospholipid bilayer. J Biol Chem. 2008;283(7):4387–94.

    Article  CAS  PubMed  Google Scholar 

  162. Bayburt TH, Vishnivetskiy SA, McLean MA, Morizumi T, Huang CC, Tesmer JJ, et al. Monomeric rhodopsin is sufficient for normal rhodopsin kinase (GRK1) phosphorylation and arrestin-1 binding. J Biol Chem. 2011;286(2):1420–8.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Divison of Molecular Therapeutics, New York State Psychiatric Institute, 1051 Riverside Drive, Unit 19, New York, NY, 10032, USA

    Wesley B. Asher Ph.D., Signe Mathiasen Ph.D., Steven G. Grinnell Ph.D. & Jonathan A. Javitch M.D., Ph.D.

  2. Department of Psychiatry, College of Physicians and Surgeons, Columbia University, 1051 Riverside Drive, Unit 19, New York, NY, 10032, USA

    Wesley B. Asher Ph.D., Signe Mathiasen Ph.D., Michael D. Holsey B.A., M.A., M.Phil., Steven G. Grinnell Ph.D. & Jonathan A. Javitch M.D., Ph.D.

  3. Department of Physiology and Cellular Biophysics, College of Physicians and Surgeons, Columbia University, 1051 Riverside Drive, Unit 19, New York, NY, 10032, USA

    Michael D. Holsey B.A., M.A., M.Phil. & Jonathan A. Javitch M.D., Ph.D.

  4. Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, 1120 15th Street, Augusta Georgia, GA, 30912, USA

    Nevin A. Lambert Ph.D.

  5. Department of Pharmacology, College of Physicians and Surgeons, Columbia University, 1051 Riverside Drive, Unit 19, New York, NY, 10032, USA

    Jonathan A. Javitch M.D., Ph.D.

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  1. Wesley B. Asher Ph.D.
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  1. Department of Neuroscience and Experimental Therapeutics, Albany Medical College, Albany, New York, USA

    Katharine Herrick-Davis

  2. Centre for Translational Pharmacology, Institute of Molecular Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom

    Graeme Milligan

  3. Department of Physiology and Biochemistry, University of Malta, Msida, Malta

    Giuseppe Di Giovanni

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Asher, W.B., Mathiasen, S., Holsey, M.D., Grinnell, S.G., Lambert, N.A., Javitch, J.A. (2017). Extreme Vetting of Dopamine Receptor Oligomerization. In: Herrick-Davis, K., Milligan, G., Di Giovanni, G. (eds) G-Protein-Coupled Receptor Dimers. The Receptors, vol 33. Humana Press, Cham. https://doi.org/10.1007/978-3-319-60174-8_5

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