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3 - GPCR-G protein fusions: Use in functional dimerization analysis

from PART II - OLIGOMERIZATION OF GPCRS

Published online by Cambridge University Press:  05 June 2012

Graeme Milligan
Affiliation:
University of Glasgow
Sandra Siehler
Affiliation:
Novartis Institute for Biomedical Research
Graeme Milligan
Affiliation:
University of Glasgow
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G Protein-Coupled Receptors
Structure, Signaling, and Physiology
, pp. 53 - 66
Publisher: Cambridge University Press
Print publication year: 2010

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References

Jacoby, E., Bouhelal, R., Gerspacher, M., and Seuwen, K. (2006) The 7 TM G-protein-coupled receptor target family. ChemMedChem. 1, 761–782.CrossRefGoogle ScholarPubMed
Huber, T., Menon, S., and Sakmar, T.P. (2008) Structural basis for ligand binding and specificity in adrenergic receptors: implications for GPCR-targeted drug discovery. Biochemistry 47, 11013–11023.CrossRefGoogle ScholarPubMed
Topiol, S., and Sabio, M. (2009). X-ray structure breakthroughs in the GPCR transmembrane region. Biochem. Pharmacol. 78, 11–20.Google Scholar
Rosenbaum, D.M., Rasmussen, S.G., and Kobilka, B.K. (2009) The structure and function of G-protein-coupled receptors. Nature 459, 356–363.CrossRefGoogle ScholarPubMed
Conn, P.J., Christopoulos, A., Lindsley, C.W. (2009) Allosteric modulators of GPCRs: a novel approach for the treatment of CNS disorders. Nat. Rev. Drug Discov. 8, 41–54.CrossRefGoogle ScholarPubMed
Milligan, G. (2007) G protein-coupled receptor dimerisation: molecular basis and relevance to function. Biochim. Biophys. Acta 1768, 825–835.CrossRefGoogle Scholar
Milligan, G. (2008) A day in the life of a G protein-coupled receptor: the contribution to function of G protein-coupled receptor dimerization. Br. J. Pharmacol. 153 Suppl 1:S216–229.CrossRefGoogle Scholar
Milligan, G. (2009) G protein-coupled receptor hetero-dimerization: contribution to pharmacology and function. Br. J. Pharmacol. [Epub ahead of print] PMID: 19309353CrossRefGoogle ScholarPubMed
Violin, J.D., and Lefkowitz, R.J. (2007) Beta-arrestin-biased ligands at seven-transmembrane receptors. Trends Pharmacol. Sci. 28, 416–422.CrossRefGoogle ScholarPubMed
Verkaar, F., Rosmalen, J.W., Blomenröhr, M., Koppen, C.J., Blankesteijn, W.M., Smits, J.F., and Zaman, G.J. (2008) G protein-independent cell-based assays for drug discovery on seven-transmembrane receptors. Biotechnol. Annu. Rev. 14, 253–274.CrossRefGoogle Scholar
Kaupmann, K., Huggel, K., Heid, J., Flor, P.J., Bischoff, S., Mickel, S.J., McMaster, G., Angst, C., Bittiger, H., Froestl, W., and Bettler, B. (1997) Expression cloning of GABA(B) receptors uncovers similarity to metabotropic glutamate receptors. Nature 386, 239–246.CrossRefGoogle ScholarPubMed
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, 683–687CrossRefGoogle ScholarPubMed
Jones, K.A., Borowsky, B., Tamm, J.A., Craig, D.A., Durkin, M.M., Dai, M., Yao, W.J., Johnson, M., Gunwaldsen, C., Huang, L.Y., Tang, C., Shen, Q., Salon, J.A., Morse, K., Laz, T., Smith, K.E., Nagarathnam, D., Noble, S.A., Branchek, T.A., and Gerald, C. (1998) GABA(B) receptors function as a heteromeric assembly of the subunits GABA(B)R1 and GABA(B)R2. Nature 396, 674–679.CrossRefGoogle ScholarPubMed
White, J.H., Wise, A., Main, M.J., Green, A., Fraser, N.J., Disney, G.H., Barnes, A.A., Emson, P., Foord, S.M., and Marshall, F.H. (1998) Heterodimerization is required for the formation of a functional GABA(B) receptor. Nature 396, 679–682.CrossRefGoogle ScholarPubMed
Maurel, D., Comps-Agrar, L., Brock, C., Rives, M.L., Bourrier, E., Ayoub, M.A., Bazin, H., Tinel, N., Durroux, 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 GPCR oligomerization. Nat. Methods 5, 561–567.CrossRefGoogle ScholarPubMed
Chabre, M., Deterre, P., and Antonny, B. (2009) The apparent cooperativity of some GPCRs does not necessarily imply dimerization. Trends Pharmacol. Sci. 30, 182–187.CrossRefGoogle Scholar
James, J.R., Oliveira, M.I., Carmo, A.M., Iaboni, A., and Davis, S.J. (2006) A rigorous experimental framework for detecting protein oligomerization using bioluminescence resonance energy transfer. Nat. Methods 3, 1001–1006.CrossRefGoogle ScholarPubMed
Pin, J.P., Neubig, R., Bouvier, M., Devi, L., Filizola, M., Javitch, J.A., Lohse, M.J., Milligan, G., Palczewski, K., Parmentier, M., and Spedding, M. (2007) International Union of Basic and Clinical Pharmacology. LXVII. Recommendations for the recognition and nomenclature of G protein-coupled receptor heteromultimers. Pharmacol. Rev. 59, 5–13.CrossRefGoogle ScholarPubMed
Ferré, S., Baler, R., Bouvier, M., Caron, M.G., Devi, L.A., Durroux, T., Fuxe, K., George, S.R., Javitch, J.A., Lohse, M.J., Mackie, K., Milligan, G., Pfleger, K.D., Pin, J.P., Volkow, N.D., Waldhoer, M., Woods, A.S., and Franco, R. (2009) Building a new conceptual framework for receptor heteromers. Nat. Chem. Biol. 5, 131–134.CrossRefGoogle ScholarPubMed
Gurevich, V.V., and Gurevich, E.V. (2008) How and why do GPCRs dimerize?Trends Pharmacol. Sci. 29, 234–240.CrossRefGoogle ScholarPubMed
Milligan, G., and Bouvier, M. (2005) Methods to monitor the quaternary structure of G protein-coupled receptors. FEBS J. 272, 2914–2925.CrossRefGoogle ScholarPubMed
Harrison, C., and Graaf, P.H. (2006) Current methods used to investigate G protein coupled receptor oligomerisation. J. Pharmacol. Toxicol. Methods 54, 26–35.CrossRefGoogle ScholarPubMed
Kearn, C.S., Blake-Palmer, K., Daniel, E., Mackie, K., and Glass, M. (2005) Concurrent stimulation of cannabinoid CB1 and dopamine D2 receptors enhances heterodimer formation: a mechanism for receptor cross-talk?Mol. Pharmacol. 67, 1697–1704.CrossRefGoogle ScholarPubMed
Waldhoer, M., Fong, J., Jones, R.M., Lunzer, M.M., Sharma, S.K., Kostenis, E., Portoghese, P.S., and Whistler, J.L. (2005) A heterodimer-selective agonist shows in vivo relevance of G protein-coupled receptor dimers. Proc. Natl. Acad. Sci. U S A 102, 9050–9055.CrossRefGoogle ScholarPubMed
Ellis, J., Pediani, J.D., Canals, M., Milasta, S., and Milligan, G. (2006) Orexin-1 receptor-cannabinoid CB1 receptor heterodimerization results in both ligand-dependent and -independent coordinated alterations of receptor localization and function. J. Biol. Chem. 281, 8812–8824.CrossRefGoogle ScholarPubMed
George, S.R., and O ' Dowd, B.F. (2007) A novel dopamine receptor signaling unit in brain: heterooligomers of D1 and D2 dopamine receptors. Scientific World Journal. 7, 58–63.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Milligan, G. (2006) G-protein-coupled receptor heterodimers: pharmacology, function and relevance to drug discovery. Drug Discov. Today 11, 541–549.CrossRefGoogle ScholarPubMed
Milligan, G., and Smith, N.J. (2007) Allosteric modulation of heterodimeric G-protein-coupled receptors. Trends Pharmacol. Sci. 28, 615–620.CrossRefGoogle ScholarPubMed
Kent, T., McAlpine, C., Sabetnia, S., and Presland, J. (2007) G-protein-coupled receptor heterodimerization: assay technologies to clinical significance. Curr. Opin. Drug Discov. Devel. 10, 580–589.Google Scholar
Dalrymple, M.B., Pfleger, K.D., and Eidne, K.A. (2008) G protein-coupled receptor dimers: functional consequences, disease states and drug targets. Pharmacol. Ther. 118, 359–371.CrossRefGoogle ScholarPubMed
Satake, H., and Sakai, T. (2008) Recent advances and perceptions in studies of heterodimerization between G protein-coupled receptors. Protein Pept. Lett. 15, 300–308.CrossRefGoogle ScholarPubMed
Panetta, R. and Greenwood, M.T. (2008) Physiological relevance of GPCR oligomerization and its impact on drug discovery. Drug Discov. Today 13, 1059–1066.CrossRefGoogle ScholarPubMed
Franco, R., Casadó, V., Cortés, A., Pérez-Capote, K., Mallol, J., Canela, E., Ferré, S., and Lluis, C. (2008) Novel pharmacological targets based on receptor heteromers. Brain Res. Rev. 58, 475–482.CrossRefGoogle ScholarPubMed
Filizola, M. (2009) Increasingly accurate dynamic molecular models of G-protein coupled receptor oligomers: Panacea or Pandora's box for novel drug discovery? Life Sci. [Epub ahead of print] PMID: 19465029
Groarke, D.A., Wilson, S., Krasel, C., and Milligan, G. (1999) Visualization of agonist-induced association and trafficking of green fluorescent protein-tagged forms of both beta-arrestin-1 and the thyrotropin-releasing hormone receptor-1. J. Biol. Chem. 274, 23263–23269.CrossRefGoogle ScholarPubMed
Ramsay, D., Bevan, N., Rees, S., and Milligan, G. (2001) Detection of receptor ligands by monitoring selective stabilization of a Renilla luciferase-tagged, constitutively active mutant, G-protein-coupled receptor. Br. J. Pharmacol. 133, 315–323.CrossRefGoogle ScholarPubMed
Zeng, F.Y., McLean, A.J., Milligan, G., Lerner, M., Chalmers, D.T., and Behan, D.P. (2003) Ligand specific up-regulation of a Renilla reniformis luciferase-tagged, structurally unstable muscarinic M3 chimeric G protein-coupled receptor. Mol. Pharmacol. 64, 1474–1484CrossRefGoogle ScholarPubMed
Vidi, P.A., and Watts, V.J. (2009) Fluorescent and bioluminescent protein-fragment complementation assays in the study of G protein-coupled receptor oligomerization and signaling. Mol. Pharmacol. 75, 733–739.CrossRefGoogle Scholar
Luker, K.E., Gupta, M., and Luker, G.D. (2009) Imaging chemokine receptor dimerization with firefly luciferase complementation. FASEB J. 23, 823–834.CrossRefGoogle ScholarPubMed
Bahia, D.S., Sartania, N., Ward, R.J., Cavalli, A., Jones, T.L., Druey, K.M., and Milligan, G. (2003) Concerted stimulation and deactivation of pertussis toxin-sensitive G proteins by chimeric G protein-coupled receptor-regulator of G protein signaling 4 fusion proteins: analysis of the contribution of palmitoylated cysteine residues to the GAP activity of RGS4. J. Neurochem. 85, 1289–1298CrossRefGoogle Scholar
Schneider, E.H., and Seifert, R. (2009) Histamine H(4) receptor-RGS fusion proteins expressed in Sf9 insect cells: A sensitive and reliable approach for the functional characterization of histamine H(4) receptor ligands. Biochem. Pharmacol. May 21 PMID: 19464266.CrossRef
Martini, L., Hastrup, H., Holst, B., Fraile-Ramos, A., Marsh, M., and Schwartz, T.W. (2002) NK1 receptor fused to beta-arrestin displays a single-component, high-affinity molecular phenotype. Mol. Pharmacol. 62, 30–37.CrossRefGoogle ScholarPubMed
Jafri, F., El-Shewy, H.M., Lee, M.H., Kelly, M., Luttrell, D.K., and Luttrell, L.M. (2006) Constitutive ERK1/2 activation by a chimeric neurokinin 1 receptor-beta-arrestin1 fusion protein. Probing the composition and function of the G protein-coupled receptor “signalsome”. J. Biol. Chem. 281, 19346–19357.CrossRefGoogle Scholar
Milligan, G., Parenty, G., Stoddart, L.A., and Lane, J.R. (2007) Novel pharmacological applications of G-protein-coupled receptor-G protein fusions. Curr. Opin. Pharmacol. 7, 521–526.CrossRefGoogle ScholarPubMed
Milligan, G., Feng, G.-J., Ward, R.J., Sartania, N., Ramsay, D., McLean, A.J., and Carrillo, J.J. (2004) G protein-coupled receptor fusion proteins in drug discovery. Current Pharmaceutical Design 10, 1989–2001.CrossRefGoogle ScholarPubMed
Suga, H., and Haga, T. (2007) Ligand screening system using fusion proteins of G protein-coupled receptors with G protein alpha subunits. Neurochem. Int. 51, 140–164.CrossRefGoogle ScholarPubMed
Bertin, B., Freissmuth, M., Jockers, R., Strosberg, A.D., and Marullo, S. (1994) Cellular signaling by an agonist-activated receptor/Gs alpha fusion protein. Proc. Natl. Acad. Sci. U S A 91, 8827–8831.CrossRefGoogle ScholarPubMed
Di Certo, M.G., Batassa, E.M., Casella, I., Serafino, A., Floridi, A., Passananti, C., Molinari, P., and Mattei, E. (2008) Delayed internalization and lack of recycling in a beta2- adrenergic receptor fused to the G protein alpha-subunit. BMC Cell Biol. 7, 9:56.CrossRefGoogle Scholar
Wise, A., Carr, I.C., and Milligan, G. (1997a) Measurement of agonist-induced guanine nucleotide turnover by the G-protein Gi1alpha when constrained within an alpha2A-adrenoceptor-Gi1alpha fusion protein. Biochem. J. 325, 17–21.CrossRefGoogle ScholarPubMed
Wise, A., Carr, I.C., Groarke, D.A., and Milligan, G. (1997b) Measurement of agonist efficacy using an alpha2A-adrenoceptor-Gi1alpha fusion protein. FEBS Lett. 419, 141–146.CrossRefGoogle ScholarPubMed
Bahia, D.S., Wise, A., Fanelli, F., Lee, M., Rees, S., and Milligan, G. (1998) Hydrophobicity of residue351 of the G protein Gi1 alpha determines the extent of activation by the alpha 2A-adrenoceptor. Biochemistry 37, 11555–11562.CrossRefGoogle Scholar
Jackson, V.N., Bahia, D.S., and Milligan, G. (1999) Modulation of relative intrinsic activity of agonists at the alpha-2A adrenoceptor by mutation of residue 351 of G protein Gi1alpha. Mol. Pharmacol. 55, 195–201.CrossRefGoogle ScholarPubMed
Fong, C.W., Bahia, D.S., Rees, S., and Milligan, G. (1998) Selective activation of a chimeric Gi1/Gs G protein alpha subunit by the human IP prostanoid receptor: analysis using agonist stimulation of high affinity GTPase activity and [35S]guanosine-5'-O-(3-thio)triphosphate binding. Mol. Pharmacol. 54, 249–257.CrossRefGoogle ScholarPubMed
Moon, H.E., Cavalli, A., Bahia, D.S., Hoffmann, M., Massotte, D., and Milligan, G. (2001) The human delta opioid receptor activates G(i1)alpha more efficiently than G(o1)alpha. J. Neurochem. 76, 1805–1813.CrossRefGoogle Scholar
Lane, J.R., Powney, B., Wise, A., Rees, S., and Milligan, G. (2007) Protean agonism at the dopamine D2 receptor: (S)-3-(3-hydroxyphenyl)-N-propylpiperidine is an agonist for activation of Go1 but an antagonist/inverse agonist for Gi1,Gi2, and Gi3. Mol. Pharmacol. 71, 1349–1359.CrossRefGoogle ScholarPubMed
Lane, J. R., Powney, B., Wise, A., Rees, S., and Milligan, G. (2008) G protein-coupling and ligand selectivity of the D2L and D3 dopamine receptors. J. Pharmacol. Exp.Therap. 325, 319–330.CrossRefGoogle Scholar
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.CrossRefGoogle ScholarPubMed
Bakker, R.A., Dees, G., Carrillo, J.J., Booth, R.G., Lopez-Gimenez, J.F., Milligan, G., Strange, P.G. and Leurs, R. (2004) Domain swapping in the human histamine H1 receptor. J. Pharmacol. Exp. Ther. 311, 131–318.CrossRefGoogle ScholarPubMed
Gouldson, P.R., Higgs, C., Smith, R.E., Dean, M.K., Gkoutos, G.V., and Reynolds, C.A. (2000) Dimerization and domain swapping in G-protein-coupled receptors: a computational study. Neuropsychopharmacology 23(4 Suppl), S60–77.CrossRefGoogle ScholarPubMed
Lee, C., Ji, I., Ryu, K., Song, Y., Conn, P.M., and Ji, T.H. (2002) Two defective heterozygous luteinizing hormone receptors can rescue hormone action. J. Biol. Chem. 277, 15795–15800.CrossRefGoogle ScholarPubMed
Carrillo, J.J., Pediani, J. and Milligan, G. (2003) Dimers of class A G protein-coupled receptors function via agonist-mediated trans-activation of associated G proteins. J. Biol. Chem. 278, 42578–42587.CrossRefGoogle Scholar
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.CrossRefGoogle Scholar
Pascal, G. and Milligan, G. (2005) Functional complementation and the analysis of opioid receptor homo-dimerization. Mol. Pharmacol. 68, 905–915.Google Scholar
Alfaras-Melainis, K., Gomes, I., Rozenfeld, R., Zachariou, V., and Devi, L. (2009) Modulation of opioid receptor function by protein-protein interactions. Front. Biosci. 14, 3594–3607.CrossRefGoogle ScholarPubMed
Pello, O.M., Martínez-Muñoz, L., Parrillas, V., Serrano, A., Rodríguez-Frade, J.M., Toro, M.J., Lucas, P., Monterrubio, M., Martínez-A, C., and Mellado, M. (2008) Ligand stabilization of CXCR4/delta-opioid receptor heterodimers reveals a mechanism for immune response regulation. Eur. J. Immunol. 38, 537–549.CrossRefGoogle ScholarPubMed
Hereld, D., and Jin, T. (2008) Slamming the DOR on chemokine receptor signaling: heterodimerization silences ligand-occupied CXCR4 and delta-opioid receptors. Eur. J. Immunol. 38, 334–337.CrossRefGoogle Scholar
Parenty, G., Appelbe, S., and Milligan, G. (2008) CXCR2 chemokine receptor antagonism enhances DOP opioid receptor function via allosteric regulation of the CXCR2-DOP receptor hetero-dimer. Biochem. J. 412, 245–256.CrossRefGoogle Scholar
Springael, J.Y., Urizar, E., Costagliola, S., Vassart, G., and Parmentier, M. (2007) Allosteric properties of G protein-coupled receptor oligomers. Pharmacol. Ther. 115, 410–418.CrossRefGoogle ScholarPubMed
Nicholls, D.J., Tomkinson, N.P., Wiley, K.E., Brammall, A., Bowers, L., Grahames, C., Gaw, A., Meghani, P., Shelton, P., Wright, T.J., and Mallinder, P.R. (2008) Identification of a putative intracellular allosteric antagonist binding-site in the CXC chemokine receptors 1 and 2. Mol. Pharmacol. 74, 1193–1202.CrossRefGoogle ScholarPubMed
Scherrer, G., Imamachi, N., Cao, Y.Q., Contet, C., Mennicken, F., O ' Donnell, D., Kieffer, B.L., and Basbaum, A.I. (2009) Dissociation of the opioid receptor mechanisms that control mechanical and heat pain. Cell 37, 1148–1159.CrossRefGoogle Scholar
Xie, Z., Bhushan, R.G., Daniels, D.J., and Portoghese, P.S. (2005) Interaction of bivalent ligand KDN21 with heterodimeric delta-kappa opioid receptors in human embryonic kidney 293 cells. Mol. Pharmacol. 68, 1079–1086.CrossRefGoogle ScholarPubMed
Zheng, Y., Akgün, E., Harikumar, K.G., Hopson, J., Powers, M.D., Lunzer, M.M., Miller, L.J., and Portoghese, P.S. (2009) Induced association of mu opioid (MOP) and type 2 cholecystokinin (CCK2) receptors by novel bivalent ligands. J. Med. Chem. 52, 247–258.CrossRefGoogle ScholarPubMed
Berque-Bestel, I., Lezoualc ' h, F., Jockers, R. (2008) Bivalent ligands as specific pharmacological tools for G protein-coupled receptor dimers. Curr. Drug Discov. Technol. 5, 312–318.CrossRefGoogle ScholarPubMed
Liu, Z., Zhang, J., and Zhang, A. (2009) Design of multivalent ligand targeting G-protein-coupled receptors. Curr. Pharm. Des. 15, 682–718.CrossRefGoogle ScholarPubMed
Milligan, G., Carrillo, J.J., and Pascal, G. (2005) Functional complementation and the analysis of GPCR dimerization. In: The G protein-coupled receptors handbook (Ed. Devi, LA) pp 267–285. Humana press, Totowa NJ.Google Scholar
Pfleger, K.D., and Eidne, K.A. (2006) Illuminating insights into protein-protein interactions using bioluminescence resonance energy transfer (BRET). Nat. Methods 3, 165–174.CrossRefGoogle Scholar

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