Roles of G‐protein‐coupled receptor dimerization

Terrillon, Sonia; Bouvier, Michel

doi:10.1038/sj.embor.7400052

Cited by 607 publications

(483 citation statements)

References 68 publications

Supporting

Mentioning

464

Contrasting

Unclassified

Order By: Relevance

“…Given the predominance of heptaspanning membrane receptors as dimers (see [4][5][6][7][8][9][10][11][12][13][14][15] for an extensive review), the interpretation of complex binding using a receptor dimer model might be more straightforward. In this case positive or negative cooperativity is naturally explained by assuming, like in the case of the enzymes, that 4 binding of the first ligand to the dimer modifies the equilibrium parameters of binding of the second ligand molecule to the dimer.…”

Section: Introductionmentioning

confidence: 99%

Useful pharmacological parameters for G-protein-coupled receptor homodimers obtained from competition experiments. Agonist–antagonist binding modulation

Casadó

Ferrada

Bonaventura

et al. 2009

Biochemical Pharmacology

View full text Add to dashboard Cite

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64

show abstract

Section: Introductionmentioning

confidence: 99%

Useful pharmacological parameters for G-protein-coupled receptor homodimers obtained from competition experiments. Agonist–antagonist binding modulation

Casadó

Ferrada

Bonaventura

et al. 2009

Biochemical Pharmacology

View full text Add to dashboard Cite

show abstract

“…Perhaps their most striking feature is that GPCR form not only functional homo-oligomers, but can also associate with other GPCR to form hetero-oligomers. Homo-and hetero-oligomers differ in their pharmacological pro- files, ligand binding affinity, and/or internalization pathways [4][5][6]. GPCR hetero-oligomerization would thus enable generation of new types of signaling units.…”

mentioning

confidence: 99%

Ligand stabilization of CXCR4/δ‐opioid receptor heterodimers reveals a mechanism for immune response regulation

et al. 2008

View full text Add to dashboard Cite

The CXCR4 chemokine receptor and the delta opioid receptor (DOR) are pertussis toxinsensitive G protein-coupled receptors (GPCR). Both are widely distributed in brain tissues and immune cells, and have key roles in inflammation processes and in pain sensation on proximal nerve endings. We show that in immune cells expressing CXCR4 and DOR, simultaneous addition of their ligands CXCL12 and [D-Pen2, DPen5]enkephalin does not trigger receptor function. This treatment does not affect ligand binding or receptor expression, nor does it promote heterologous desensitization. Our data indicate that CXCR4 and DOR form heterodimeric complexes that are dynamically regulated by the ligands. This is compatible with a model in which GPCR oligomerization leads to suppression of signaling, promoting a dominant negative effect. Knockdown of CXCR4 and DOR signaling by heterodimerization might have repercussions on physiological and pathological processes such as inflammation, pain sensation and HIV-1 infection.Supporting Information for this article is available at http://www.wiley-vch.de/contents/jc_2040/2008/37630_s.pdf See accompanying article: http://dx.doi.org/10.1002/eji200738101 IntroductionThe G protein-coupled receptors (GPCR) represent the largest, most diverse family of transmembrane receptors expressed in the body. They act through G proteins to regulate intracellular processes including cell adhesion, migration and proliferation [1]. Studies show that the GPCR can function as oligomers [2,3]. Perhaps their most striking feature is that GPCR form not only functional homo-oligomers, but can also associate with other GPCR to form hetero-oligomers. Homo-and hetero-oligomers differ in their pharmacological pro- files, ligand binding affinity, and/or internalization pathways [4][5][6]. GPCR hetero-oligomerization would thus enable generation of new types of signaling units. Opioid and chemokine receptors are members of the Ga i protein-linked GPCR. These receptors and their ligands are expressed in neurons and glial cells, and in immune system cells such as lymphocytes, monocytes and neutrophils [7]. They share the same microenvironment in many physiological situations and are essential for inflammation processes. Chemokine receptors promote immune cell migration to and adhesion at the inflammation site, whereas opioid receptors reduce pain sensation on proximal nerve endings. Opioid receptors can also regulate the immune response, as they alter antibody responses, cell-mediated immunity, phagocytic activity, adhesion and chemotaxis [8][9][10][11]. Opioids also prevent leukocyte movement toward chemokine gradients [12], and cross-desensitization is described between opioid and chemokine receptors [8,10]. The CCR5 chemokine receptor can form heterodimers with each of the three opioid receptor subtypes (l, d, and j) [8,10].CXCR4, the most widely expressed chemokine receptor [13], is crucial for correct lymphocyte trafficking [14], hematopoiesis, and development [15][16][17]. It is also a coreceptor for T-tropic HIV strains [1...

show abstract

“…A growing number of in vitro evidence supports the hypothesis that many GPCRs assemble in homo-or heterodimeric/oligomeric complexes [3]. The functional role of such supra-molecular complexes is still unclear and may vary depending on the GPCR type [18,20].…”

Section: Discussionmentioning

confidence: 99%

“…Emerging evidence suggests that many GPCRs exist as homo-and/or hetero-assemblies of two or more monomers [2,3]. The thromboxane A 2 receptor (TP) is not an exception, as in vitro evidence has shown that the a and b isoforms of this GPCR form homodimers and heterodimers independently from their functional state (this study and the papers from [4,5], as well as heterodimers with other prostanoid GPCRs [6,7].…”

Section: Introductionmentioning

confidence: 88%

Light on the structure of thromboxane A2 receptor heterodimers

Fanelli

Mauri

Capra

et al. 2011

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

The structure-based design of a mutant form of the thromboxane A 2 prostanoid receptor (TP) was instrumental in characterizing the structural determinants of the hetero-dimerization process of this G protein coupled receptor (GPCR). The results suggest that the heterodimeric complexes between the TPa and b isoforms are characterized by contacts between hydrophobic residues in helix 1 from both monomers. Functional characterization confirms that TPa-TPb hetero-dimerization serves to regulate TPa function through agonist-induced internalization, with important implications in cardiovascular homeostasis. The integrated approach employed in this study can be adopted to gain structural and functional insights into the dimerization/oligomerization process of all GPCRs for which the structural model of the monomer can be achieved at reasonable atomic resolution.

show abstract

Roles of G‐protein‐coupled receptor dimerization

Cited by 607 publications

References 68 publications

Useful pharmacological parameters for G-protein-coupled receptor homodimers obtained from competition experiments. Agonist–antagonist binding modulation

Useful pharmacological parameters for G-protein-coupled receptor homodimers obtained from competition experiments. Agonist–antagonist binding modulation

Ligand stabilization of CXCR4/δ‐opioid receptor heterodimers reveals a mechanism for immune response regulation

Light on the structure of thromboxane A2 receptor heterodimers

Contact Info

Product

Resources

About