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Science 288 (5463): 154-157

Copyright © 2000 by the American Association for the Advancement of Science

Receptors for Dopamine and Somatostatin: Formation of Hetero-Oligomers with Enhanced Functional Activity

Magalie Rocheville, 1 Daniela C. Lange, 2 Ujendra Kumar, 1 Shutish C. Patel, 3 Ramesh C. Patel, 2 Yogesh C. Patel 1*

Somatostatin and dopamine are two major neurotransmitter systems that share a number of structural and functional characteristics. Somatostatin receptors and dopamine receptors are colocalized in neuronal subgroups, and somatostatin is involved in modulating dopamine-mediated control of motor activity. However, the molecular basis for such interaction between the two systems is unclear. Here, we show that dopamine receptor D2R and somatostatin receptor SSTR5 interact physically through hetero-oligomerization to create a novel receptor with enhanced functional activity. Our results provide evidence that receptors from different G protein (heterotrimeric guanine nucleotide binding protein)-coupled receptor families interact through oligomerization. Such direct intramembrane association defines a new level of molecular crosstalk between related G protein-coupled receptor subfamilies.

1 Fraser Laboratories, Departments of Medicine, Pharmacology, Therapeutics, Neurology, and Neurosurgery, McGill University and Royal Victoria Hospital, Montreal, Quebec H3A 1A1, Canada.
2 Departments of Physics and Chemistry, Clarkson University, Potsdam, NY 13699, USA.
3 VA Connecticut Healthcare System and New England Biomedical Research Center, Newington, CT 06111, USA.
*   To whom correspondence should be addressed. E-mail: yogesh.patel{at}muhc.mcgill.ca


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The Alternatively Spliced {Delta}e13 Transcript of the Rabbit Calcitonin Receptor Dimerizes with the C1a Isoform and Inhibits Its Surface Expression.
T. Seck, R. Baron, and W. C. Horne (2003)
J. Biol. Chem. 278, 23085-23093
   Abstract »    Full Text »    PDF »
Evidence for CD4-enchanced Signaling through the Chemokine Receptor CCR5.
R. Staudinger, S. K. Phogat, X. Xiao, X. Wang, D. S. Dimitrov, and S. Zolla-Pazner (2003)
J. Biol. Chem. 278, 10389-10392
   Abstract »    Full Text »    PDF »
Heterodimerization of alpha 2A- and beta 1-Adrenergic Receptors.
J. Xu, J. He, A. M. Castleberry, S. Balasubramanian, A. G. Lau, and R. A. Hall (2003)
J. Biol. Chem. 278, 10770-10777
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Homo- and Hetero-oligomerization of Thyrotropin-releasing Hormone (TRH) Receptor Subtypes. DIFFERENTIAL REGULATION OF beta -ARRESTINS 1 AND 2.
A. C. Hanyaloglu, R. M. Seeber, T. A. Kohout, R. J. Lefkowitz, and K. A. Eidne (2002)
J. Biol. Chem. 277, 50422-50430
   Abstract »    Full Text »    PDF »
Inhibitory interactions between 5-HT3 and P2X channels in submucosal neurons.
C. Barajas-Lopez, L. M. Montano, and R. Espinosa-Luna (2002)
Am J Physiol Gastrointest Liver Physiol 283, G1238-G1248
   Abstract »    Full Text »    PDF »
Ligand-dependent Inhibition of Oligomerization at the Human Thyrotropin Receptor.
R. Latif, P. Graves, and T. F. Davies (2002)
J. Biol. Chem. 277, 45059-45067
   Abstract »    Full Text »    PDF »
Quantitative Assessment of beta 1- and beta 2-Adrenergic Receptor Homo- and Heterodimerization by Bioluminescence Resonance Energy Transfer.
J.-F. Mercier, A. Salahpour, S. Angers, A. Breit, and M. Bouvier (2002)
J. Biol. Chem. 277, 44925-44931
   Abstract »    Full Text »    PDF »
Prediction of heterodimerization interfaces of G-protein coupled receptors with a new subtractive correlated mutation method.
M. Filizola, O. Olmea, and H. Weinstein (2002)
Protein Eng. Des. Sel. 15, 881-885
   Abstract »    Full Text »    PDF »
Dopamine Activates Noradrenergic Receptors in the Preoptic Area.
C. A. Cornil, J. Balthazart, P. Motte, L. Massotte, and V. Seutin (2002)
J. Neurosci. 22, 9320-9330
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Internalization and recycling of 5-HT2A receptors activated by serotonin and protein kinase C-mediated mechanisms.
S. Bhattacharyya, S. Puri, R. Miledi, and M. M. Panicker (2002)
PNAS 99, 14470-14475
   Abstract »    Full Text »    PDF »
The Extracellular N-terminal Domain and Transmembrane Domains 1 and 2 Mediate Oligomerization of a Yeast G Protein-coupled Receptor.
M. C. Overton and K. J. Blumer (2002)
J. Biol. Chem. 277, 41463-41472
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Constitutive Agonist-independent CCR5 Oligomerization and Antibody-mediated Clustering Occurring at Physiological Levels of Receptors.
H. Issafras, S. Angers, S. Bulenger, C. Blanpain, M. Parmentier, C. Labbe-Jullie, M. Bouvier, and S. Marullo (2002)
J. Biol. Chem. 277, 34666-34673
   Abstract »    Full Text »    PDF »
beta 1/beta 2-Adrenergic Receptor Heterodimerization Regulates beta 2-Adrenergic Receptor Internalization and ERK Signaling Efficacy.
C. Lavoie, J.-F. Mercier, A. Salahpour, D. Umapathy, A. Breit, L.-R. Villeneuve, W.-Z. Zhu, R.-P. Xiao, E. G. Lakatta, M. Bouvier, et al. (2002)
J. Biol. Chem. 277, 35402-35410
   Abstract »    Full Text »    PDF »
Electrophysiological Evidence for Expression of Glycine Receptors in Freshly Isolated Neurons from Nucleus Accumbens.
G. Martin and G. R. Siggins (2002)
J. Pharmacol. Exp. Ther. 302, 1135-1145
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Dimerization and Phosphorylation of Thyrotropin-releasing Hormone Receptors Are Modulated by Agonist Stimulation.
C.-C. Zhu, L. B. Cook, and P. M. Hinkle (2002)
J. Biol. Chem. 277, 28228-28237
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Dopamine Modulates the Function of Group II and Group III Metabotropic Glutamate Receptors in the Substantia Nigra Pars Reticulata.
M. Wittmann, M. J. Marino, and P. J. Conn (2002)
J. Pharmacol. Exp. Ther. 302, 433-441
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Monitoring of Ligand-independent Dimerization and Ligand-induced Conformational Changes of Melatonin Receptors in Living Cells by Bioluminescence Resonance Energy Transfer.
M. A. Ayoub, C. Couturier, E. Lucas-Meunier, S. Angers, P. Fossier, M. Bouvier, and R. Jockers (2002)
J. Biol. Chem. 277, 21522-21528
   Abstract »    Full Text »    PDF »
G Protein-Coupled Receptor Allosterism and Complexing.
A. Christopoulos and T. Kenakin (2002)
Pharmacol. Rev. 54, 323-374
   Abstract »    Full Text »    PDF »
Heterodimerization of Somatostatin and Opioid Receptors Cross-modulates Phosphorylation, Internalization, and Desensitization.
M. Pfeiffer, T. Koch, H. Schroder, M. Laugsch, V. Hollt, and S. Schulz (2002)
J. Biol. Chem. 277, 19762-19772
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Importance of the {gamma}-Aminobutyric AcidB Receptor C-Termini for G-Protein Coupling.
S. Grunewald, B. J. Schupp, S. R. Ikeda, R. Kuner, F. Steigerwald, H.-C. Kornau, and G. Kohr (2002)
Mol. Pharmacol. 61, 1070-1080
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Ligand binding to somatostatin receptors induces receptor-specific oligomer formation in live cells.
R. C. Patel, U. Kumar, D. C. Lamb, J. S. Eid, M. Rocheville, M. Grant, A. Rani, T. Hazlett, S. C. Patel, E. Gratton, et al. (2002)
PNAS 99, 3294-3299
   Abstract »    Full Text »    PDF »

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