Journal of Biological Chemistry
Volume 277, Issue 38, 20 September 2002, Pages 34666-34673
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MECHANISMS OF SIGNAL TRANSDUCTION
Constitutive Agonist-independent CCR5 Oligomerization and Antibody-mediated Clustering Occurring at Physiological Levels of Receptors*

https://doi.org/10.1074/jbc.M202386200Get rights and content
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Although homo-oligomerization has been reported for several G protein-coupled receptors, this phenomenon was not studied at low concentrations of receptors. Furthermore, it is not clear whether homo-oligomerization corresponds to an intrinsic property of nascent receptors or if it is a consequence of receptor activation. Here CCR5 receptor oligomerization was studied by bioluminescence resonance energy transfer (BRET) in cells expressing physiological levels of receptors. A strong energy transfer could be observed, in the absence of ligands, in whole cells and in both endoplasmic reticulum and plasma membrane subfractions, supporting the hypothesis of a constitutive oligomerization that occurs early after biosynthesis. No change in BRET was observed upon agonist binding, indicating that the extent of oligomerization is unrelated to the activation state of the receptor. In contrast, a robust increase of BRET, induced by a monoclonal antibody known to promote receptor clustering, suggests that microaggregation of preformed receptor homo-oligomers can occur. Taken together, our data indicate that constitutive receptor homo-oligomerization has a biologically relevant significance and might be involved in the process of receptor biosynthesis.

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*

This work was supported by grants from the Agence Nationale pour la Recherche sur le SIDA the Association pour la Recherche sur le Cancer, the Actions de Recherche Concertées of the Communauté Française de Belgique, and the Canadian Institute for Health Research.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available athttp://www.jbc.org) contains additional text and one figure.

Recipient of a fellowship from the Association pour la Recherche sur la Polyarthrite Rhumatoı̈de.

Holder of a Canada Research Chair in Molecular and Cellular Pharmacology.