Oligomers of D2 dopamine receptors
Tóm tắt
There is increasing evidence that G protein-coupled receptors form oligomers and that this might be important for their function. We have studied this phenomenon for the D2 dopamine receptor and have shown—using a variety of biochemical and biophysical techniques—that this receptor forms dimers or higher-order oligomers. Using ligand-binding studies, we have also found evidence that this oligomer formation has functional relevance. Thus, for the receptor expressed in either CHO cells or Sf 9 insect cells, the binding properties of several radioligands (in saturation, competition, and dissociation assays) do not conform to those expected for a monomeric receptor with a single binding site. We propose that the receptors exist in oligomers with homotropic and heterotropic negatively cooperative interactions between ligands.
Tài liệu tham khảo
Angers S., Salahpour A., and Bouvier M. (2002) Dimerization: an emerging concept for G protein-coupled receptor ontogeny and function. Annu. Rev. Pharmacol. Toxicol. 42, 409–435.
Armstrong D. and Strange P. G. (2001) Dopamine D2 receptor dimer formation: evidence from ligand binding. J. Biol. Chem. 276, 22621–22629.
Bray D. and Duke T. (2004) Conformational spread: the propagation of allosteric states in large multiprotein complexes. Annu. Rev. Biophys. Biomol. Struct. 33, 53–73.
Chatterjee T. K., Scott C. E., Vazquez D. M., and Bhatnagar R. K. (1988) Interaction of [3H]spiperone with rat striatal dopamine D-2 receptors: kinetic evidence for antagonist-induced formation of ternary complex. Mol. Pharmacol. 33, 402–413.
Cordeaux Y., Nickolls S. A., Flood L. A., Graber S. G., and Strange P. G. (2001) Agonist regulation of D(2) dopamine receptor/G protein interaction. Evidence for agonist selection of G protein subtype. J. Biol. Chem. 276, 28667–28675.
Cox M. A., Jenh C. H., Gonsiorek W., Fine J., Narula S. K., Zavodny P. J., and Hipkin R. W. (2001) Human interferon-inducible 10-kDa protein and human interferon-inducible T cell alpha chemoattractant are allotopic ligands for human CXCR3: differential binding to receptor states. Mol. Pharmacol. 59, 707–715.
Devi L. A. (2001) Heterodimerization of G-protein-coupled receptors: pharmacology, signaling and trafficking. Trends Pharmacol. Sci. 22, 532–537.
Duthey B., Caudron S., Perroy J., Bettler B., Fagni L., Pin J. P., and Prezeau L. (2002) A single subunit (GB2) is required for G-protein activation by the heterodimeric GABA(B) receptor. J. Biol. Chem. 277, 3236–3241.
Fotiadis D., Liang Y., Filipek S., Saperstein D. A., Engel A., and Palczewski K. (2004) The G protein-coupled receptor rhodopsin in the native membrane. FEBS Lett. 564, 281–288.
Franco R., Casado V., Ciruela F., Mallol J., Lluis C., and Canela E. I. (1996) The cluster-arranged cooperative model: a model that accounts for the kinetics of binding to A1 adenosine receptors. Biochemistry 35, 3007–3015.
Gazi L., Lopez-Gimenez J. F., and Strange P. G. (2002) Formation of oligomers by G protein-coupled receptors. Curr. Opin. Drug Discov. Dev. 5, 756–763.
Gazi L., Lopez-Gimenez J. F., Rudiger M. P., and Strange P. G. (2003a) 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. 270, 3928–3938.
Gazi L., Wurch T., Lopez-Gimenez J. F., Pauwels P. J., and Strange P. G. (2003b) Pharmacological analysis of a dopamine D(2Short):G((o) fusion protein expressed in Sf9 cells. FEBS Lett. 545, 155–160.
Hall H., Wedel I., Halldin C., Kopp J., and Farde L. (1990) Comparison of the in vitro receptor binding properties of N-[3H]methylspiperone and [3H]raclopride to rat and human brain membranes. J. Neurochem. 55, 2048–2057.
Hirschberg B. T. and Schimerlik M. I. (1994) A kinetic model for oxotremorine M binding to recombinant porcine m2 muscarinic receptors expressed in Chinese hamster ovary cells. J. Biol. Chem. 269, 26127–26135.
Limbird L. E. and Lefkowitz R. J. (1976) Negative cooperativity among beta-adrenergic receptors in frog erythrocyte membranes. J. Biol. Chem. 251, 5007–5014.
Malmberg A., Jerning E., and Mohell N. (1996) Critical reevaluation of spiperone and benzamide binding to dopamine D2 receptors: evidence for identical binding sites. Eur. J. Pharmacol. 303, 123–128.
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 ligand binding analyzed by computer-assisted curve fitting. J. Biol. Chem. 260, 7410–7421.
Ng G. Y., O’Dowd B. F., Caron M., Dennis M., Brann M. R., and George S. R. (1994) Phosphorylation and palmitoylation of the human D2L dopamine receptor in Sf9 cells. J. Neurochem. 63, 1589–1595.
Nickolls S. A. and Strange P. G. (2003) Interaction of the D2short dopamine receptor with G proteins: analysis of receptor/G protein selectivity. Biochem. Pharmacol. 65, 1139–1150.
Park P. S. and Wells J. W. (2004) Oligomeric potential of the M2 muscarinic cholinergic receptor. J. Neurochem. 90, 537–548.
Park P. S., Sum C. S., Pawagi A. B., and Wells J. W. (2002) Cooperativity and oligomeric status of cardiac muscarinic cholinergic receptors. Biochemistry 41, 5588–5604.
Salahpour A., Bonin H., Bhalla S., Petaja-Repo U., and Bouvier M. (2003) Biochemical characterization of beta2-adrenergic receptor dimers and oligomers. Biol. Chem. 384, 117–123.
Seeman P., Guan H. C., Civelli O., Van Tol H. H., Sunahara R. K., and Niznik H. B. (1992) The cloned dopamine D2 receptor reveals different densities for dopamine receptor antagonist ligands. Implications for human brain positron emission tomography. Eur. J. Pharmacol. 227, 139–146.
Sourjik V. and Berg H. C. (2004) Functional interactions between receptors in bacterial chemotaxis. Nature 428, 437–441.
Sum C. S., Pyo N., and Wells J. W. (2001) Apparent capacity of cardiac muscarinic receptors for different radiolabeled antagonists. Biochem. Pharmacol. 62, 829–851.
Terai M., Hidaka K., and Nakamura Y. (1989) Comparison of [3H]YM-09151-2 with [3H]spiperone and [3H]raclopride for dopamine d-2 receptor binding to rat striatum. Eur. J. Pharmacol. 173, 177–182.
Theodorou A. E., Jenner P., and Marsden C. D. (1983) Cation specificity of 3H-sulpiride binding involves alteration in the number of striatal binding sites. Life Sci. 32, 1243–1254.
Vile J. M., D’Souza U. M., and Strange P. G. (1995) [3H]Nemonapride and [3H]spiperone label equivalent numbers of D2 and D3 dopamine receptors in a range of tissues and under different conditions. J. Neurochem. 64, 940–943.
Vivo M. and Strange P. G. (2003a) Effect of sodium ions on ligand bindig to the D2short dopamine receptor. Br. J. Pharmacol. Abstr. 1, 69P.
Vivo M. and Strange P. G. (2003b) Effect of sodium ions on [3H]nemonapride dissociation from the D2short dopamine receptor. Br. J. Pharmacol. Abstr. 1, 171P.
Wreggett K. A. and Wells J. W. (1995) Cooperativity manifest in the binding properties of purified cardiac muscarinic receptors. J. Biol. Chem. 270, 22488–22499.
Wurch T., Matsumoto A. and Pauwels P. J. (2001) Agonist-independent and -dependent oligomerization of dopamine D(2) receptors by fusion to fluorescent proteins. FEBS Lett. 507, 109–113.