Circulation Research. 2004;94:17-27
doi: 10.1161/01.RES.0000110420.68526.19
doi: 10.1161/01.RES.0000110420.68526.19
© 2004 American Heart Association, Inc.
Reviews |
G Protein–Coupled Receptor Oligomerization
Implications for G Protein Activation and Cell Signaling
From the Department of Biology, Syracuse University, Syracuse, NY.
Correspondence to Gerda E. Breitwieser, PhD, Department of Biology, Syracuse University, 122 Lyman Hall, 108 College Place, Syracuse, NY 13244. E-mail gebreitw{at}syr.edu
This Review is part of a thematic series on Heterodimerization of Signaling Molecules, which includes the following articles:
Regulation of G Protein–Coupled Receptor Signaling by Scaffold Proteins
G Protein–Coupled Receptor Oligomerization: Implications for G Protein Activation and Cell Signaling
Multitasking RGS Protein in the Heart: The Next Therapeutic Target?
Gerda Breitwieser Editor
The cardiovascular system is richly endowed with G protein–coupled receptors (GPCRs), members of the largest family of plasma membrane-localized receptors. During the last 10 years, it has become increasingly clear that many, if not all, GPCRs function in oligomeric complexes, as either homo- or hetero-oligomers. This review explores the mechanistic implications of GPCR dimerization and/or oligomerization on receptor activation and interactions with G proteins. The effects of GPCR oligomerization on receptor pharmacology, GPCR-mediated signaling, and potential contributions to GPCR crosstalk will be considered in the context of receptors important in the cardiovascular system. Our evolving understanding of the structural and functional consequences of GPCR oligomerization may provide novel and more selective sites for pharmacological tuning of cardiovascular function.
Key Words: G protein–coupled receptors • oligomerization • heterodimerization • signal transduction • G protein activation
This article has been cited by other articles:
 |
|
 |
|
  L. Szidonya, M. Cserzo, and L. Hunyady Dimerization and oligomerization of G-protein-coupled receptors: debated structures with established and emerging functions J. Endocrinol., March 1, 2008; 196(3): 435 - 453. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Roth, C. Nasarre, S. Dirrig-Grosch, D. Aunis, G. Cremel, P. Hubert, and D. Bagnard Transmembrane Domain Interactions Control Biological Functions of Neuropilin-1 Mol. Biol. Cell, February 1, 2008; 19(2): 646 - 654. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Brock, N. Oueslati, S. Soler, L. Boudier, P. Rondard, and J.-P. Pin Activation of a Dimeric Metabotropic Glutamate Receptor by Intersubunit Rearrangement J. Biol. Chem., November 9, 2007; 282(45): 33000 - 33008. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Xia, C. C. Zhou, S. M. Ramin, and R. E. Kellems Angiotensin Receptors, Autoimmunity, and Preeclampsia J. Immunol., September 15, 2007; 179(6): 3391 - 3395. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Ellis, J. D. Pediani, M. Canals, S. Milasta, and G. Milligan Orexin-1 Receptor-Cannabinoid CB1 Receptor Heterodimerization Results in Both Ligand-dependent and -independent Coordinated Alterations of Receptor Localization and Function J. Biol. Chem., December 15, 2006; 281(50): 38812 - 38824. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Santi, G. Ferreira, B. Yang, V.-R. Gazula, A. Butler, A. Wei, L. K. Kaczmarek, and L. Salkoff Opposite regulation of Slick and Slack K+ channels by neuromodulators. J. Neurosci., May 10, 2006; 26(19): 5059 - 5068. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. R. Gross and G. J. Gross Ligand triggers of classical preconditioning and postconditioning Cardiovasc Res, May 1, 2006; 70(2): 212 - 221. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Leger, S. L. Jacques, J. Badar, N. C. Kaneider, C. K. Derian, P. Andrade-Gordon, L. Covic, and A. Kuliopulos Blocking the Protease-Activated Receptor 1-4 Heterodimer in Platelet-Mediated Thrombosis Circulation, March 7, 2006; 113(9): 1244 - 1254. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Goin and N. M. Nathanson Quantitative Analysis of Muscarinic Acetylcholine Receptor Homo- and Heterodimerization in Live Cells: REGULATION OF RECEPTOR DOWN-REGULATION BY HETERODIMERIZATION J. Biol. Chem., March 3, 2006; 281(9): 5416 - 5425. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Milasta, J. Pediani, S. Appelbe, S. Trim, M. Wyatt, P. Cox, M. Fidock, and G. Milligan Interactions between the Mas-Related Receptors MrgD and MrgE Alter Signalling and Trafficking of MrgD Mol. Pharmacol., February 1, 2006; 69(2): 479 - 491. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Storez, M. G. H. Scott, H. Issafras, A. Burtey, A. Benmerah, O. Muntaner, T. Piolot, M. Tramier, M. Coppey-Moisan, M. Bouvier, et al. Homo- and Hetero-oligomerization of {beta}-Arrestins in Living Cells J. Biol. Chem., December 2, 2005; 280(48): 40210 - 40215. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. J. Song and P. M. Hinkle Regulated Dimerization of the Thyrotropin-Releasing Hormone Receptor Affects Receptor Trafficking But Not Signaling Mol. Endocrinol., November 1, 2005; 19(11): 2859 - 2870. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. H. de Castro, R. A. Souza dos Santos, A. J. Ferreira, M. Bader, N. Alenina, and A. Pinto de Almeida Evidence for a Functional Interaction of the Angiotensin-(1-7) Receptor Mas With AT1 and AT2 Receptors in the Mouse Heart Hypertension, October 1, 2005; 46(4): 937 - 942. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Pascal and G. Milligan Functional Complementation and the Analysis of Opioid Receptor Homodimerization Mol. Pharmacol., September 1, 2005; 68(3): 905 - 915. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Wilson, G. Wilkinson, and G. Milligan The CXCR1 and CXCR2 Receptors Form Constitutive Homo- and Heterodimers Selectively and with Equal Apparent Affinities J. Biol. Chem., August 5, 2005; 280(31): 28663 - 28674. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Thevenin, T. Lazarova, M. F. Roberts, and C. R. Robinson Oligomerization of the fifth transmembrane domain from the adenosine A2A receptor Protein Sci., August 1, 2005; 14(8): 2177 - 2186. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Q. Gomes da Silva, R. A. Sousa dos Santos, and M. A. Peliky Fontes Blockade of Endogenous Angiotensin-(1-7) in the Hypothalamic Paraventricular Nucleus Reduces Renal Sympathetic Tone Hypertension, August 1, 2005; 46(2): 341 - 348. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Leppanen, S. Stowell, O. Blixt, and R. D. Cummings Dimeric Galectin-1 Binds with High Affinity to {alpha}2,3-Sialylated and Non-sialylated Terminal N-Acetyllactosamine Units on Surface-bound Extended Glycans J. Biol. Chem., February 18, 2005; 280(7): 5549 - 5562. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-C. Zhong, D.-Y. Huang, G.-F. Liu, H.-Y. Jin, Y.-M. Yang, Y.-F. Li, X.-H. Song, and K. Du Effects of all-trans retinoic acid on orphan receptor APJ signaling in spontaneously hypertensive rats Cardiovasc Res, February 15, 2005; 65(3): 743 - 750. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Wilson, A. M. Roche, E. Kostetskaia, and E. M. Smyth Dimerization of the Human Receptors for Prostacyclin and Thromboxane Facilitates Thromboxane Receptor-mediated cAMP Generation J. Biol. Chem., December 17, 2004; 279(51): 53036 - 53047. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-C. Zhong, D.-Y. Huang, Y.-M. Yang, Y.-F. Li, G.-F. Liu, X.-H. Song, and K. Du Upregulation of Angiotensin-Converting Enzyme 2 by All-trans Retinoic Acid in Spontaneously Hypertensive Rats Hypertension, December 1, 2004; 44(6): 907 - 912. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Liang, D. Fotiadis, T. Maeda, A. Maeda, A. Modzelewska, S. Filipek, D. A. Saperstein, A. Engel, and K. Palczewski Rhodopsin Signaling and Organization in Heterozygote Rhodopsin Knockout Mice J. Biol. Chem., November 12, 2004; 279(46): 48189 - 48196. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-Q. Ma, E. F. Plow, and J.-G. Geng P-selectin binding to P-selectin glycoprotein ligand-1 induces an intermediate state of {alpha}M{beta}2 activation and acts cooperatively with extracellular stimuli to support maximal adhesion of human neutrophils Blood, October 15, 2004; 104(8): 2549 - 2556. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. V. B. Pinheiro, A. C. Simoes e Silva, W. O. Sampaio, R. D. de Paula, E. P. Mendes, E. D. Bontempo, J. B. Pesquero, T. Walther, N. Alenina, M. Bader, et al. Nonpeptide AVE 0991 Is an Angiotensin-(1-7) Receptor Mas Agonist in the Mouse Kidney Hypertension, October 1, 2004; 44(4): 490 - 496. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Medina, D. Perdomo, and J. Bubis The Hydrodynamic Properties of Dark- and Light-activated States of n-Dodecyl {beta}-D-Maltoside-solubilized Bovine Rhodopsin Support the Dimeric Structure of Both Conformations J. Biol. Chem., September 17, 2004; 279(38): 39565 - 39573. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Aburi and P. E. Smith Modeling and simulation of the human {delta} opioid receptor Protein Sci., August 1, 2004; 13(8): 1997 - 2008. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. P. Brothers, A. Cornea, J. A. Janovick, and P. M. Conn Human Loss-of-Function Gonadotropin-Releasing Hormone Receptor Mutants Retain Wild-Type Receptors in the Endoplasmic Reticulum: Molecular Basis of the Dominant-Negative Effect Mol. Endocrinol., July 1, 2004; 18(7): 1787 - 1797. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. A. Eckardt Abscisic Acid Signal Transduction: Function of G Protein-Coupled Receptor 1 in Arabidopsis PLANT CELL, June 1, 2004; 16(6): 1353 - 1354. [Full Text] [PDF]
|
|