title: Heterologous regulation of Mu-opioid (MOP) receptor mobility in the membrane of SH-SY5Y cells.
abstract: The dynamic organization of G protein-coupled receptors in the plasma membrane is suspected of playing a role in their function. The regulation of the diffusion mode of the mu-opioid (MOP) receptor was previously shown to be agonist-specific. Here we investigate the regulation of MOP receptor diffusion by heterologous activation of other G protein-coupled receptors and characterize the dynamic properties of the MOP receptor within the heterodimer MOP/neuropeptide FF (NPFF2) receptor. The data show that the dynamics and signaling of the MOP receptor in SH-SY5Y cells are modified by the activation of α2-adrenergic and NPFF2 receptors, but not by the activation of receptors not described to interact with the opioid receptor. By combining, for the first time, fluorescence recovery after photobleaching at variable radius experiments with bimolecular fluorescence complementation, we show that the MOP/NPFF2 heterodimer adopts a specific diffusion behavior that corresponds to a mix of the dynamic properties of both MOP and NPFF2 receptors. Altogether, the data suggest that heterologous regulation is accompanied by a specific organization of receptors in the membrane.
authors.affiliation: From the Institut de Pharmacologie et Biologie Structurale, UMR5089 CNRS/Université de Toulouse, 31077 Toulouse, France.
authors.forename: Kévin
authors.initials: K
authors.lastname: Carayon
authors.affiliation: From the Institut de Pharmacologie et Biologie Structurale, UMR5089 CNRS/Université de Toulouse, 31077 Toulouse, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Moulédous
authors.affiliation: From the Institut de Pharmacologie et Biologie Structurale, UMR5089 CNRS/Université de Toulouse, 31077 Toulouse, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Combedazou
authors.affiliation: From the Institut de Pharmacologie et Biologie Structurale, UMR5089 CNRS/Université de Toulouse, 31077 Toulouse, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Mazères
authors.affiliation: From the Institut de Pharmacologie et Biologie Structurale, UMR5089 CNRS/Université de Toulouse, 31077 Toulouse, France.
authors.forename: Evert
authors.initials: E
authors.lastname: Haanappel
authors.affiliation: From the Institut de Pharmacologie et Biologie Structurale, UMR5089 CNRS/Université de Toulouse, 31077 Toulouse, France laurence.salome@ipbs.fr.
authors.forename: Laurence
authors.initials: L
authors.lastname: Salomé
authors.affiliation: From the Institut de Pharmacologie et Biologie Structurale, UMR5089 CNRS/Université de Toulouse, 31077 Toulouse, France catherine.mollereau-manaute@ipbs.fr.
authors.forename: Catherine
authors.initials: C
authors.lastname: Mollereau
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003000:Clonidine / Q000494:pharmacology; D004058:Diffusion; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D036681:Fluorescence Recovery After Photobleaching; D005456:Fluorescent Dyes; D005786:Gene Expression Regulation; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009478:Neuropeptide Y / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D055503:Protein Multimerization; D021381:Protein Transport / Q000187:drug effects*; D020239:Receptor Cross-Talk / Q000187:drug effects*; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics / Q000378:metabolism*; D018013:Receptors, Neuropeptide / Q000235:genetics / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000701:Analgesics, Opioid; D005456:Fluorescent Dyes; D009478:Neuropeptide Y; D009842:Oligopeptides; D018341:Receptors, Adrenergic, alpha-2; D018013:Receptors, Neuropeptide; D017450:Receptors, Opioid, mu; C083929:neuropeptide FF receptor; C105455:neuropeptide FF, Tyr(1)-N-methyl-Phe(3)-; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D003000:Clonidine
keywords: Bimolecular Fluorescence Complementation (BiFC); Fluorescence Recovery after Photobleaching (FRAP); G Protein-coupled Receptor (GPCR); Opiate Opioid; Plasma Membrane; Protein-Protein Interaction