title: Constitutive agonist-independent CCR5 oligomerization and antibody-mediated clustering occurring at physiological levels of receptors.
abstract: 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.
authors.affiliation: Department of Cell Biology, Cochin Institute, INSERM U-567, CNRS UMR-8104 and University René-Descartes, Paris 75014, France.
authors.forename: Hassan
authors.initials: H
authors.lastname: Issafras
authors.forename: Stéphane
authors.initials: S
authors.lastname: Angers
authors.forename: Sébastien
authors.initials: S
authors.lastname: Bulenger
authors.forename: Cédric
authors.initials: C
authors.lastname: Blanpain
authors.forename: Marc
authors.initials: M
authors.lastname: Parmentier
authors.forename: Catherine
authors.initials: C
authors.lastname: Labbé-Jullié
authors.forename: Michel
authors.initials: M
authors.lastname: Bouvier
authors.forename: Stefano
authors.initials: S
authors.lastname: Marullo
mesh_terms: D001704:Biopolymers; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004735:Energy Transfer; D005455:Fluorescent Antibody Technique; D006801:Humans; D008163:Luminescent Measurements; D019713:Receptors, CCR5 / Q000819:agonists / Q000378:metabolism*
chemical_list: D001704:Biopolymers; D019713:Receptors, CCR5