BRET and time-resolved FRET strategy to study GPCR oligomerization: From cell lines toward native tissues

Frontiers in Endocrinology

Volumn 3, Issue JUL, 2012, Pages

  Cottet, Martin ^a,b   Faklaris, Orestis ^a,b   Maurel, Damien ^a,b   Scholler, Pauline ^a,b   Doumazane, Etienne ^a,b   Trinquet, Eric ^c   Pin, Jean Philippe ^a,b   Durroux, Thierry ^a,b  

^a CNRS   (France)

^b INSERM   (France)

^c Cisbio Bioassays ^*  (France)

Author keywords

BRET; Fluorescence; Fluorescent ligand; FRET; G protein coupled receptor; Oligomer; Time resolved FRET

Indexed keywords

EID: 84873155972     PISSN: None     EISSN: 16642392     Source Type: Journal    
DOI: 10.3389/fendo.2012.00092     Document Type: Review

References (123)

1. Achour, L., Kamal, M., Jock-ers, R., and Marullo, S. (2011). Using quantitative BRET to assess G protein-coupled receptor homo- and heterodimerization. Methods Mol. Biol. 756, 183-200.
2. Albizu, L., Balestre, M. N., Breton, C., Pin, J. P., Manning, M., Mouillac, B., Barberis, C., and Durroux, T. (2006). Probing the existence of G protein-coupled receptor dimers by positive and negative ligand-dependent cooperative binding. Mol. Pharmacol. 70, 1783-1791.
3. Albizu, L., Cottet, M., Kralikova, M., Stoev, S., Seyer, R., Brabet, I., Roux, T., Bazin, H., Bourrier, E., Lamar-que, L., Breton, C., Rives, M. L., Newman, A., Javitch, J., Trinquet, E., Manning, M., Pin, J. P., Mouillac, B., and Durroux, T. (2010). Time-resolved FRET between GPCR ligands reveals oligomers in native tissues. Nat. Chem. Biol. 6, 587-594.
4. Albizu, L., Holloway, T., González-Maeso, J., and Sealfon, S. C. (2011). Functional crosstalk and heteromer-ization of serotonin 5-HT2A and dopamine D2 receptors. Neurophar-macology 61, 770-777.
5. Albizu, L., Teppaz, G., Seyer, R., Bazin, H., Ansanay, H., Manning, M., Mouillac, B., and Durroux, T. (2007). Toward efficient drug screening by homogeneous assays based on the development of new fluorescent vasopressin and oxytocin receptor ligands. J. Med. Chem. 50, 4976-4985.
6. Angers, S., Salahpour, A., Joly, E., Hilairet, S., Chelsky, D., Dennis, M., and Bouvier, M. (2000). Detection of beta 2-adrenergic receptor dimer-ization in living cells using biolumi-nescence resonance energy transfer (BRET). Proc. Natl Acad. Sci. U.S.A. 97,3684-3689.
7. Arcemisbéhère, L., Sen, T., Boudier, L., Balestre, M. N., Gaibelet, G., Detouillon, E., Orcel, H., Mendre, C., Rahmeh, R., Granier, S., Vivès, C., Fieschi, F., Damian, M., Durroux, T., Banères, J. L., and Mouillac, B. (2010). Leukotriene BLT2 receptor monomers activate the G(i2) GTP-binding protein more efficiently than dimers. J. Biol Chem. 285, 6337-6347.
8. Armstrong, D., and Strange, P. G. (2001). Dopamine D2 receptor dimer formation: evidence from ligand binding. J. Biol. Chem. 276, 22621-22629.
9. Ayoub, M. A., and Pfleger, K. D. (2010). Recent advances in bioluminescence resonance energy transfer technologies to study GPCR heteromeriza-tion. Curr. Opin. Pharmacol. 10, 44-52.
10. Ayoub, M. A., Trinquet, E., Pfleger, K. D., and Pin, J. P. (2010). Differential association modes of the thrombin receptor PAR1 with Galphai1, Gal-pha12, and beta-arrestin 1. FASEB J. 24, 3522-3535.
11. Bacart, J., Corbel, C., Jockers, R., Bach, S., and Couturier, C. (2008). The BRET technology and its application to screening assays. Biotechnol. J. 3, 311-324.
12. Bakker, R. A., Dees, G., Carrillo, J. J., Booth, R. G., López-Gimenez, J. E, Milligan, G., Strange, P. G., and Leurs, R. (2004). Domain swapping in the human histamine H1 receptor. J. Pharmacol. Exp. Ther. 311, 131-138.
13. Bazin, H., Trinquet, E., and Mathis, G. (2002). Time resolved amplification of cryptate emission: a versatile technology to trace biomolecular interactions. J. Biotechnol. 82, 233-250.
14. Birdsall, N. J. (2010). Class A GPCR heterodimers: evidence from binding studies. Trends Pharmacol. Sci. 31, 499-508.
15. Boute, N., Jockers, R., and Issad, T. (2002). The use of resonance energy transfer in high-throughput screening: BRET versus FRET. Trends Pharmacol. Sci. 23,351-354.
16. Breton, B., Sauvageau, É., Zhou, J., Bonin, H., Le Gouill, C., and Bouvier, M. (2010). Multiplexing of multicolor bioluminescence resonance energy transfer. Biophys. J. 99, 4037-4046.
17. Brock, C., Oueslati, N., Soler, S., Boudier, L., Rondard, P., and Pin, J. P. (2007). Activation of a dimeric metabotropic glutamate receptor by intersubunit rearrangement. J. Biol. Chem. 282,33000-33008.
18. Brun, M. A., Griss, R., Reymond, L., Tan, K. T., Piguet, J., Peters, R. J., Vogel, H., and Johnsson, K. (2011). Semisynthesis of fluorescent metabolite sensors on cell surfaces. J. Am. Chem. Soc. 133, 16235-16242.
19. Brun, M. A., Tan, K. T., Nakata, E., Hin-ner, M. J., and Johnsson, K. (2009). Semisynthetic fluorescent sensor proteins based on self-labeling protein tags. J. Am. Chem. Soc. 131, 5873-5884.
20. Carriba, P., Navarro, G., Ciruela, F., Ferré, S., Casadó, V., Agnati, L., Cortés, A., Mallol, J., Fuxe, K., Canela, E. I., Lluís, C., and Franco, R. (2008). Detection of heteromer-ization of more than two proteins by sequential BRET-FRET. Nat. Methods 5, 727-733.
21. Carrillo, J. J., Lopez-Gimenez, J. F., and Milligan, G. (2004). Multiple interactions between transmem-brane helices generate the oligomeric alpha1b-adrenoceptor. Mol. Pharmacol. 66, 1123-1137.
22. Chabre, M., Deterre, P., and Antonny, B. (2009). The apparent cooperativ-ity of some GPCRs does not necessarily imply dimerization. Trends Pharmacol. Sci. 30,182-187.
23. Chabre, M., and le Maire, M. (2005). Monomeric G-protein-coupled receptor as a functional unit. Biochemistry 44, 9395-9403.
24. Ciruela, F., Ferré, S., Casadó, V., Cortés, A., Cunha, R. A., Lluis, C., and Franco, R. (2006). Heterodimeric adenosine receptors: a device to regulate neurotransmitter release. Cell Mol. Life Sci. 63, 2427-2431.
25. Comps-Agrar, L., Kniazeff, J., Nørskov-Lauritsen, L., Maurel, D., Gassmann, M., Gregor, N., Prézeau, L., Bettler, B., Durroux, T., Trinquet, E., and Pin, J. P. (2011a). The oligomeric state sets GABA(B) receptor signalling efficacy. EMBO J.30,2336-2349.
26. Comps-Agrar, L., Maurel, D., Rondard, P., Pin, J. P., Trinquet, E., and Prézeau, L. (2011b). Cell-surface protein-protein interaction analysis with time-resolved FRET and SNAP-tag technologies: application to G protein-coupled receptor oligomerization. Methods Mol. Biol. 756, 201-214.
27. Cottet, M., Albizu, L., Comps-Agrar, L., Trinquet, E., Pin, J. P., Mouillac, B., and Durroux, T. (2011). Time resolved FRET strategy with fluorescent ligands to analyze receptor interactions in native tissues: application to GPCR oligomerization. Methods Mol. Biol. 746, 373-387.
28. Coulon, V., Audet, M., Homburger, V., Bockaert, J., Fagni, L., Bouvier, M., and Perroy, J. (2008). Subcel-lular imaging of dynamic protein interactions by bioluminescence resonance energy transfer. Biophys. J. 94, 1001-1009.
29. Cvejic, S., and Devi, L. A. (1997). Dimerization of the delta opioid receptor: implication for a role in receptor internalization. J. Biol. Chem. 272,26959-26964.
30. De, A., Ray, P., Loening, A. M., and Gambhir, S. S. (2009). BRET3: a red-shifted bioluminescence resonance energy transfer (BRET)-based integrated platform for imaging protein-protein interactions from single live cells and living animals. FASEB J. 23, 2702-2709.
31. De Genst, E., Silence, K., Decanniere, K., Conrath, K., Loris, R., Kinne, J., Muyldermans, S., and Wyns, L. (2006). Molecular basis for the preferential cleft recognition by dromedary heavy-chain antibodies. Proc. Natl. Acad. Sci. U.S.A. 103, 4586-4591.
32. Delille, H. K., Becker, J. M., Burkhardt, S., Bleher, B., Terstappen, G. C., Schmidt, M., Meyer, A. H., Unger, L., Marek, G. J., and Mezler, M. (2012). Heterocomplex formation of 5-HT(2A)-mGlu(2) and its relevance for cellular signaling cascades. Neu-ropharmacology 62, 2183-2190.
33. Dorsch, S., Klotz, K. N., Engel-hardt, S., Lohse, M. J., and Bünemann, M. (2009). Analysis of receptor oligomerization by FRAP microscopy. Nat. Methods 6, 225-230.
34. Doumazane, E., Scholler, P., Zwier, J. M., Eric, T., Rondard, P., and Pin, J. P. (2011). A new approach to analyze cell surface protein complexes reveals specific heterodimeric metabotropic glutamate receptors. FASEB J. 25, 66-77.
35. Durroux, T. (2005). Principles: a model for the allosteric interactions between ligand binding sites within a dimeric GPCR. Trends Pharmacol. Sci. 26, 376-384.
36. Durroux, T., Peter, M., Turcatti, G., Chollet, A., Balestre, M. N., Barberis, C., and Seyer, R. (1999). Fluorescent pseudo-peptide linear vasopressin antagonists: design, synthesis, and applications. J. Med. Chem. 42, 1312-1319.
37. Duthey, B., Caudron, S., Perroy, J., Bettler, B., Fagni, L., Pin, J. P., and Prézeau, L. (2002). A single subunit (GB2) is required for G-protein activation by the heterodimeric GABA(B) receptor. J. Biol. Chem. 277, 3236-3241.
38. Förster, T. (1948). Zwischenmolekulare Energiewanderung und Fluoreszenz. Ann. Phys. (Leipzig) 2, 55-75.
39. Fotiadis, D., Jastrzebska, B., Philippsen, A., Müller, D. J., Palczewski, K., and Engel, A. (2006). Structure of the rhodopsin dimer: a working model for G-protein-coupled receptors. Curr. Opin. Struct. Biol. 16, 252-259.
40. Fotiadis, D., Liang, Y., Filipek, S., Saperstein, D. A., Engel, A., and Palczewski, K. (2003). Atomic-force microscopy: rhodopsin dimers in native disc membranes. Nature 421, 127-128.
41. Fribourg, M., Moreno, J. L., Holloway, T., Provasi, D., Baki, L., Mahajan, R., Park, G., Adney, S. K., Hatcher, C., Eltit, J. M., Ruta, J. D., Albizu, L., Li, Z., Umali, A., Shim, J., Fabiato. A., MacKerell, A. D., Brezina, V., Sealfon, S. C., Filizola, M., González-Maeso, J., and Logothetis, D. E. (2011). Decoding the signaling of a GPCR het-eromeric complex reveals a unifying mechanism of action of antipsychotic drugs. Cell 147, 1011-1023.
42. Galvez, T., Parmentier, M. L., Joly, C., Malitschek, B., Kaupmann, K., Kuhn, R., Bittiger, H., Froestl, W., Bettler, B., and Pin, J. P. (1999). Mutage-nesis and modeling of the GABAB receptor extracellular domain support a venus flytrap mechanism for ligand binding. J. Biol. Chem. 274, 13362-13369.
43. Galvez, T., Prezeau, L., Milioti, G., Franek, M., Joly, C., Froestl, W., Bettler, B., Bertrand, H. O., Blahos, J., and Pin, J. P. (2000). Mapping the agonist-binding site of GABAB type 1 subunit sheds light on the activation process of GABAB receptors. J. Biol. Chem. 275,41166-41174.
44. Gautier, A., Juillerat, A., Heinis, C., Cor-rêa, I. R., Kindermann, M., Beaufils, F., and Johnsson, K. (2008). An engineered protein tag for multiprotein labeling in living cells. Chem. Biol. 15, 128-136.
45. Gautier, A., Nakata, E., Lukinavicius, G., Tan, K. T., and Johnsson, K. (2009). Selective cross-linking of interacting proteins using self-labeling tags. J. Am. Chem. Soc. 131,17954-17962.
46. Goin, J. C., and Nathanson, N. M. (2006). Quantitative analysis of muscarinic acetylcholine receptor homo - and heterodimerization in live cells: regulation of receptor down-regulation by heterodimerization. J. Biol. Chem. 281, 5416-5425.
47. González-Maeso, J., Ang, R. L., Yuen, T., Chan, P., Weisstaub, N. V., López-Giménez, J. F., Zhou, M., Okawa, Y., Callado, L. F., Milligan, G., Gingrich, J. A., Filizola, M., Meana, J. J., and Sealfon, S. C. (2008). Identification of a serotonin/glutamate receptor complex implicated in psychosis. Nature 452, 93-97.
48. Goudet, C., Kniazeff, J., Hlavackova, V., Malhaire, F., Maurel, D., Acher, E, Blahos, J., Prézeau, L., and Pin, J. P. (2005). Asymmetric functioning of dimeric metabotropic glutamate receptors disclosed by positive allosteric modulators. J. Biol. Chem. 280,24380-24385.
49. Grant, M., Collier, B., and Kumar, U. (2004). Agonist-dependent dissociation of human somatostatin receptor 2 dimers. A role in receptor trafficking. J. Biol. Chem. 279, 36179-36183.
50. Gronemeyer, T., Chidley, C., Juillerat, A., Heinis, C., and Johnsson, K. (2006). Directed evolution of O6-alkylguanine-DNA alkyltransferase for applications in protein labeling. Protein Eng. Des. Sel. 19, 309-316.
51. Gronemeyer, T., Godin, G., and Johns-son, K. (2005). Adding value to fusion proteins through covalent labelling. Curr. Opin. Biotechnol. 16,453-458.
52. Guo, W., Urizar, E., Kralikova, M., Mobarec, J. C., Shi, L., Filizola, M., and Javitch, J. A. (2008). Dopamine D2 receptors form higher order oligomers at physiological expression levels. EMBOJ. 27, 2293-2304.
53. Hamdan, F. F., Audet, M., Garneau, P., Pelletier, J., and Bouvier, M. (2005). High-throughput screening of G protein-coupled receptor antagonists using a bioluminescence resonance energy transfer 1-based beta-arrestin2 recruitment assay. J. Biomol. Screen. 10, 463-475.
54. Han, Y., Moreira, I. S., Urizar, E., Wein-stein, H., and Javitch, J. A. (2009). Allosteric communication between protomers of dopamine class A GPCR dimers modulates activation. Nat. Chem. Biol. 5, 688-695.
55. Harmsen, M. M., and De Haard, H. J. (2007). Properties, production, and applications of camelid single-domain antibody fragments. Appl. Microbiol. Biotechnol. 77, 13-22.
56. Hebert, T. E., Moffett, S., Morello, J. P., Loisel, T. P., Bichet, D. G., Barret, C., and Bouvier, M. (1996). A peptide derived from a beta2-adrenergic receptor transmembrane domain inhibits both receptor dimer-ization and activation. J. Biol. Chem. 271,16384-16392.
57. Hern, J. A., Baig, A. H., Mashanov, G. I., Birdsall, B., Corrie, J. E., Lazareno, S., Molloy, J. E., and Birdsall, N. J. (2010). 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. 107, 2693-2698.
58. Hlavackova, V., Goudet, C., Kniazeff, J., Zikova, A., Maurel, D., Vol, C., Tro-janova, J., Prézeau, L., Pin, J. P., and Blahos, J. (2005). Evidence for asingle heptahelical domain being turned on upon activation of a dimeric GPCR. EMBOJ. 24, 499-509.
59. Ilien, B., Franchet, C., Bernard, P., Morisset, S., Weill, C. O., Bour-guignon, J. J., Hibert, M., and Galzi, J. L. (2003). Fluorescence resonance energy transfer to probe human M1 muscarinic receptor structure and drug binding properties. J. Neu-rochem. 85, 768-778.
60. Ilien, B., Glasser, N., Clamme, J. P., Didier, P., Piemont, E., Chinnap-pan, R., Daval, S. B., Galzi, J. L., and Mely, Y (2009). Pirenzepine promotes the dimerization of muscarinic M1 receptors through a three-step binding process. J. Biol. Chem. 284, 19533-19543.
61. Jones, S. A., Shim, S. H., He, J., and Zhuang, X. (2011). Fast, three-dimensional super-resolution imaging of live cells. Nat. Methods 8, 499-508.
62. Jordan, B. A., and Devi, L. A. (1999). G-protein-coupled receptor heterodimerization modulates receptor function. Nature 399, 697-700.
63. Ju, W., Morishita, W., Tsui, J., Gai-etta, G., Deerinck, T. J., Adams, S. R., Garner, C. C., Tsien, R. Y., Ellisman, M. H., and Malenka, R. C. (2004). Activity-dependent regulation of dendritic synthesis and trafficking of AMPA receptors. Nat. Neurosci. 7, 244-253.
64. Juillerat, A., Gronemeyer, T., Keppler, A., Gendreizig, S., Pick, H., Vogel, H., and Johnsson, K. (2003). Directed evolution of O6-alkylguanine-DNA alkyltransferase for efficient labeling of fusion proteins with small molecules in vivo. Chem. Biol. 10, 313-317.
65. Juillerat, A., Heinis, C., Sielaff, I., Barnikow, J., Jaccard, H., Kunz, B., Terskikh, A., and Johnsson, K. (2005). Engineering substrate specificity of O6-alkylguanine-DNA alkyltransferase for specific protein labeling in living cells. Chembiochem 6, 1263-1269.
66. Kasai, R. S., Suzuki, K. G., Prossnitz, E. R., Koyama-Honda, I., Nakada, C., Fujiwara, T. K., and Kusumi, A. (2011). Full characterization of GPCR monomer-dimer dynamic equilibrium by single molecule imaging.J. Cell Biol. 192,463-480.
67. Kaupmann, K., Malitschek, B., Schuler, V., Heid, J., Froestl, W., Beck, P., Mosbacher, J., Bischoff, S., Kulik, A., Shigemoto, R., Karschin, A., and Bettler, B. (1998). GABA(B)-receptor subtypes assemble into functional heteromeric complexes. Nature 396, 683-687.
68. Keppler, A., Gendreizig, S., Gronemeyer, T., Pick, H., Vogel, H., and Johnsson, K. (2003). A general method for the covalent labeling of fusion proteins with small molecules in vivo. Nat. Biotechnol. 21,86-89.
69. Keppler, A., Pick, H., Arrivoli, C., Vogel, H., and Johnsson, K. (2004). Labeling of fusion proteins with synthetic fluorophores in live cells. Proc. Natl. Acad. Sci. U.S.A. 101,9955-9959.
70. Kniazeff, J., Bessis, A. S., Maurel, D., Ansanay, H., Prézeau, L., and Pin, J. P. (2004). Closed state of both binding domains of homodimeric mGlu receptors is required for full activity. Nat. Struct. Mol. Biol. 11, 706-713.
71. Loening, A. M., Fenn, T. D., Wu, A. M., and Gambhir, S. S. (2006). Consensus guided mutagenesis of Renilla luciferase yields enhanced stability and light output. Protein Eng. Des. Sel. 19,391-400.
72. Lohse, M. J., Nuber, S., and Hoffmann, C. (2012). Fluores-cence/bioluminescence resonance energy transfer techniques to study G-protein-coupled receptor activation and signaling. Pharmacol. Rev. 64,299-336.
73. Lopez-Gimenez, J. F., Canals, M., Pedi-ani, J. D., and Milligan, G. (2007). The alpha1b-adrenoceptor exists as a higher-order oligomer: effective oligomerization is required for receptor maturation, surface delivery, and function. Mol. Pharmacol. 71, 1015-1029.
74. Maggio, R., Vogel, Z., and Wess, J. (1993). Coexpression studies with mutant muscarinic/adrenergic receptors provide evidence for intermolec-ular cross-talk between G-protein-linked receptors. Proc. Natl. Acad. Sci. U.S.A. 90,3103-3107.
75. Mathis, G. (1995). Probing molecular interactions with homogeneous techniques based on rare earth cryptates and fluorescence energy transfer. Clin. Chem.41, 1391-1397.
76. Mattera, R., Pitts, B. J., Entman, M. L., and Birnbaumer, L. (1985). Guanine nucleotide regulation of a mammalian myocardial muscarinic receptor system. Evidence for homo-and heterotropic cooperativity in lig-and binding analyzed by computer-assisted curve fitting. J. Biol. Chem. 260,7410-7421.
77. Maurel, D., Comps-Agrar, L., Brock, C., Rives, M. L., Bourrier, E., Ayoub, M. A., Bazin, H., Tinel, N., Dur-roux, T., Prézeau, L., Trinquet, E., and Pin, J. P. (2008). Cell-surface protein-protein interaction analysis with time-resolved FRET and SNAP-tag technologies: application to GPCRoligomerization. Nat. Methods 5, 561-567.
78. Maurel, D., Kniazeff, J., Mathis, G., Trinquet, E., Pin, J. P., and Ansanay, H. (2004). Cell surface detection of membrane protein interaction with homogeneous time-resolved fluorescence resonance energy transfer technology. Anal. Biochem. 329, 253-262.
79. McVey, M., Ramsay, D., Kellett, E., Rees, S., Wilson, S., Pope, A. J., and Milli-gan, G. (2001). Monitoring receptor oligomerization using time-resolved fluorescence resonance energy transfer and bioluminescence resonance energy transfer. The human delta-opioid receptor displays constitutive oligomerization at the cell surface, which is not regulated by receptor occupancy.J. Biol. Chem. 276,14092-14099.
80. Meyer, B. H., Segura, J. M., Martinez, K. L., Hovius, R., George, N., Johnsson, K., and Vogel, H. (2006). FRET imaging reveals that functional neurokinin-1 receptors are monomeric and reside in membrane microdomains of live cells. Proc. Natl. Acad.Sci. U.S.A. 103,2138-2143.
81. Milligan, G. (2010). The role of dimeri-sation in the cellular trafficking of G-protein-coupled receptors. Curr. Opin. Pharmacol. 10, 23-29.
82. Monnier, C., Tu, H., Bourrier, E., Vol, C., Lamarque, L., Trinquet, E., Pin, J. P., and Rondard, P. (2011). Trans-activation between 7TM domains: implication in heterodimeric GABAB receptor activation. EMBO J. 30, 32-42.
83. Monnot, C., Bihoreau, C., Conchon, S., Curnow, K. M., Corvol, P., and Clauser, E. (1996). Polar residues in the transmembrane domains of the type 1 angiotensin II receptor are required for binding and coupling. Reconstitution of the binding site by co-expression of two deficient mutants. J. Biol. Chem. 271, 1507-1513.
84. Ng, G. Y., O'Dowd, B. F., Lee, S. P., Chung, H. T., Brann, M. R., See-man, P., and George, S. R. (1996). Dopamine D2 receptor dimers and receptor-blocking peptides. Biochem. Biophys. Res. Commun. 227, 200-204.
85. Orcel, H., Albizu, L., Perkovska, S., Dur-roux, T., Mendre, C., Ansanay, H., Mouillac, B., and Rabié, A. (2009). Differential coupling of the vaso-pressin V1b receptor through com-partmentalization within the plasma membrane. Mol. Pharmacol. 75, 637-647.
86. Pagano, A., Rovelli, G., Mosbacher, J., Lohmann, T., Duthey, B., Stauffer, D., Ristig, D., Schuler, V., Meigel, I., Lampert, C., Stein, T., Prezeau, L., Blahos, J., Pin, J., Froestl, W., Kuhn, R., Heid, J., Kaupmann, K., and Bettler,B. (2001). C-terminalinteraction is essential for surface trafficking but not for heteromeric assembly of GABA(b) receptors. J. Neurosci. 21, 1189-1202.
87. Paila, Y. D., Kombrabail, M., Krish-namoorthy, G., and Chattopad-hyay, A. (2011). Oligomerization of the serotonin(1A) receptor in live cells: a time-resolved fluorescence anisotropy approach. J. Phys. Chem. B 115,11439-11447.
88. Patel, R. C., Kumar, U., Lamb, D. C., Eid, J. S., Rocheville, M., Grant, M., Rani, A., Hazlett, T., Patel, S. C., Gratton, E., and Patel, Y. C. (2002). Ligand binding to somatostatin receptors induces receptor-specific oligomer formation in live cells. Proc. Natl. Acad. Sci. U.S.A. 99, 3294-3299.
89. Pellissier, L. P., Barthet, G., Gaven, E, Cassier, E., Trinquet, E., Pin, J. P., Marin, P., Dumuis, A., Bock-aert, J., Banères, J. L., and Claeysen, S. (2011). G protein activation by serotonin type 4 receptor dimers: evidence that turning on two protomers is more efficient. J. Biol. Chem. 286, 9985-9997.
90. Pfleger, K. D., Seeber, R. M., and Eidne, K. A. (2006). Bioluminescence resonance energy transfer (BRET) for the real-time detection of protein-protein interactions. Nat. Protoc. 1, 337-345.
91. Pin, J. P., Galvez, T., and Prézeau, L. (2003). Evolution, structure, and activation mechanism of family 3/C G-protein-coupled receptors. Pharmacol. Ther. 98, 325-354.
92. Rahmeh, R., Damian, M., Cottet, M., Orcel, H., Mendre, C., Durroux, T., Sharma, K. S., Durand, G., Pucci, B., Trinquet, E., Zwier, J. M., Deupi, X., Bron, P., Baneres, J. L., Mouillac, B., and Granier, S. (2012). Structural insights into biased G protein-coupled receptor signaling revealed by fluorescence spectroscopy. Proc. Natl. Acad. Sci. U.S.A. 109, 6733-6738.
93. Rajapakse, H. E., Gahlaut, N., Mohan-dessi, S., Yu, D., Turner, J. R., and Miller, L. W. (2010). Time-resolved luminescence resonance energy transfer imaging of protein-protein interactions in living cells. Proc. Natl. Acad. Sci. U.S.A. 107, 13582-13587.
94. Ramsay, D., Carr, I. C., Pediani, J., Lopez-Gimenez, J. F., Thurlow, R., Fidock, M., and Milligan, G. (2004). High-affinity interactions between human alpha1A-adrenoceptor C-terminal splice variants produce homo- and heterodimers but do not generate the alpha1L-adrenoceptor. Mol. Pharmacol. 66, 228-239.
95. Rios, C. D., Jordan, B. A., Gomes, I., and Devi, L. A. (2001). G-protein-coupled receptor dimerization: modulation of receptor function. Pharmacol. Ther. 92,71-87.
96. Rivero-Müller, A., Chou, Y. Y., Ji, I., Lajic, S., Hanyaloglu, A. C., Jonas, K., Rahman, N., Ji, T. H., and Huh-taniemi,I. (2010). Rescue of defective G protein-coupled receptor function in vivo by intermolecular cooperation. Proc. Natl. Acad. Sci. U.S.A. 107, 2319-2324.
97. Roess, D. A., Horvat, R. D., Munnelly, H., and Barisas, B. G. (2000). Lute-inizing hormone receptors are self-associated in the plasma membrane. Endocrinology 141,4518-4523.
98. Romano, C., Yang, W. L., and O'Malley, K. L. (1996). Metabotropic glutamate receptor 5 is a disulfide-linked dimer. J. Biol. Chem. 271,28612-28616.
99. Rondard, P., Liu, J., Huang, S., Malhaire, E, Vol, C., Pinault, A., Labesse, G., and Pin, J. P. (2006). Coupling of agonist binding to effector domain activation in metabotropic glutamate-like receptors. J. Biol. Chem. 281, 24653-24661.
100. Rovira, X., Pin, J. P., and Giraldo, J. (2010). The asymmetric/symmetric activation of GPCR dimers as a possible mechanistic rationale for multiple signalling pathways. Trends Pharmacol. Sci. 31, 15-21.
101. Salahpour, A., Angers, S., and Bouvier, M. (2000). Functional significance of oligomerization of G-protein-coupled receptors. Trends Endocrinol. Metab. 11, 163-168.
102. Salahpour, A., Angers, S., Mercier, J. F., Lagacé, M., Marullo, S., and Bouvier, M. (2004). Homodimerization of the beta2-adrenergic receptor as a prerequisite for cell surface targeting. J. Biol. Chem. 279, 33390-33397.
103. Selvin, P. R. (2002). Principles and biophysical applications of lanthanide-based probes. Annu. Rev. Biophys. Biomol. Struct. 31, 275-302.
104. Springael, J. Y., Le Minh, P. N., Urizar, E., Costagliola, S., Vassart, G., and Par-mentier, M. (2006). Allosteric modulation of binding properties between units of chemokine receptor homo-and hetero-oligomers. Mol. Pharmacol. 69, 1652-1661.
105. Sun, X., Zhang, A., Baker, B., Sun, L., Howard, A., Buswell, J., Maurel, D., Masharina, A., Johnsson, K., Noren, C. J., Xu, M. Q., and Corrêa, I. R. (2011). Development of SNAP-tag fluorogenic probes for wash-free fluorescence imaging. Chembiochem 12, 2217-2226.
106. Tahtaoui, C., Guillier, F., Klotz, P., Galzi, J. L., Hibert, M., and Ilien, B. (2005). On the use of nonfluorescent dye labeled ligands in FRET-based receptor binding studies. J. Med. Chem. 48, 7847-7859.
107. Terrillon, S., Barberis, C., and Bouvier, M. (2004). Heterodimerization of V1a and V2 vasopressin receptors determines the interaction with beta-arrestin and their trafficking patterns. Proc. Natl. Acad. Sci. U.S.A. 101, 1548-1553.
108. Terrillon, S., and Bouvier, M. (2004). Roles of G-protein-coupled receptor dimerization. EMBO Rep. 5, 30-34.
109. Terrillon, S., Durroux, T., Mouillac, B., Breit, A., Ayoub, M. A., Taulan, M., Jockers, R., Barberis, C., and Bouvier, M. (2003). Oxytocin and vasopressin V1a and V2 receptors form constitutive homo- and heterodimers during biosynthesis. Mol. Endocrinol. 17, 677-691.
110. Trinquet, E., Fink, M., Bazin, H., Grillet, E, Maurin, F., Bourrier, E., Ansanay, H., Leroy, C., Michaud, A., Durroux, T., Maurel, D., Malhaire, F., Goudet, C., Pin, J. P., Naval, M., Hernout, O., Chrétien, F., Chapleur, Y., and Mathis, G. (2006). D-myo-inositol 1-phosphate as a surrogate of D-myo-inositol 1,4,5-tris phosphate to monitor G protein-coupled receptor activation. Anal. Biochem. 358, 126-135.
111. Urizar, E., Montanelli, L., Loy, T., Bonomi, M., Swillens, S., Gales, C., Bouvier, M., Smits, G., Vassart, G., and Costagliola, S. (2005). Gly-coprotein hormone receptors: link between receptor homodimerization and negative cooperativity. EMBO J. 24,1954-1964.
112. van Rijn, R. M., Chazot, P. L., Shen-ton, E C., Sansuk, K., Bakker, R. A., and Leurs, R. (2006). Oligomer-ization of recombinant and endoge-nously expressed human histamine H(4) receptors. Mol. Pharmacol. 70, 604-615.
113. Vassart, G. (2010). An in vivo demonstration of functional G protein-coupled receptor dimers. Proc. Natl. Acad. Sci. U.S.A. 107,1819-1820.
114. Ward, R. J., Pediani, J. D., and Milli-gan, G. (2011). Heteromultimeriza-tion of cannabinoid CB(1) receptor and orexin OX(1) receptor generates a unique complex in which both pro-tomers are regulated by orexin A. J. Biol. Chem. 286, 37414-37428.
115. White, 1. E, Grodnitzky, J., Louis, J. M., Trinh, L. B., Shiloach, J., Gutierrez, J., Northup, J. K., and Grisshammer, R. (2007). Dimerization of the class A G protein-coupled neurotensin receptor NTS1 alters G protein interaction. Proc. Natl. Acad. Sci. U.S.A. 104, 12199-12204.
116. Wilson, S., Wilkinson, G., and Mil-ligan, G. (2005). The CXCR1 and CXCR2 receptors form constitutive homo- and heterodimers selectively and with equal apparent affinities. J. Biol. Chem. 280, 28663-28674.
117. Wreggett, K. A., and Wells, J. W. (1995). Cooperativity manifest in the binding properties of purified cardiac mus-carinic receptors. J. Biol. Chem. 270, 22488-22499.
118. Xu, J., Corneillie, T. M., Moore, E. G., Law, G. L., Butlin, N. G., and Raymond, K. N. (2011). Octadentate cages of Tb(III) 2-hydroxyisophthalamides: a new standard for luminescent lanthanide labels.J.Am. Chem. Soc. 133, 19900-19910.
119. Zhang, Y., So, M. K., Loening, A. M., Yao, H., Gambhir, S. S., and Rao, J. (2006). HaloTag protein-mediated site-specific conjugation of biolumi-nescent proteins to quantum dots. Angew. Chem. Int. Ed. Engl. 45, 4936-4940.
120. Zheng, J., Trudeau, M. C., and Zagotta, W. N. (2002). Rod cyclic nucleotide-gated channels have a stoichiome-try of three CNGA1 subunits and one CNGB1 subunit. Neuron 36, 891-896.
121. Zürn, A., Klenk, C., Zabel, U., Reiner, S., Lohse, M. J., and Hoffmann, C. (2010). Site-specific, orthogonal labeling of proteins in intact cells with two small biarsenical flu-orophores. Bioconjug Chem. 21, 853-859.
122. Zwier, J., Poole, R., Ansanay, H., Fink, M., and Trinquet, E. (2011). Methode de detection de l'internalisation de proteines membranaires/verfahren zum nach-weis von membranproteininternal-isierung/method for detecting membrane protein internalization. EPO Patent: EP 2329272 A2.
123. Zwier, J. M., Roux, T., Cottet, M., Dur-roux, T., Douzon, S., Bdioui, S., Gregor, N., Bourrier, E., Oueslati, N., Nicolas, L., Tinel, N., Bois-seau, C., Yverneau, P., Charrier-Savournin, F., Fink, M., and Trinquet, E. (2010). A fluorescent ligand-binding alternative using Tag-lite(R) technology. J. Biomol. Screen. 15, 1248-1259.