title: Regulation of β2-adrenergic receptor maturation and anterograde trafficking by an interaction with Rab geranylgeranyltransferase: modulation of Rab geranylgeranylation by the receptor.
abstract: Previous reports by us and others demonstrated that G protein-coupled receptors interact functionally with Rab GTPases. Here, we show that the β(2)-adrenergic receptor (β(2)AR) interacts with the Rab geranylgeranyltransferase α-subunit (RGGTA). Confocal microscopy showed that β(2)AR co-localizes with RGGTA in intracellular compartments and at the plasma membrane. Site-directed mutagenesis revealed that RGGTA binds to the L(339)L(340) motif in the β(2)AR C terminus known to be involved in the transport of the receptor from the endoplasmic reticulum to the cell surface. Modulation of the cellular levels of RGGTA protein by overexpression or siRNA-mediated knockdown of the endogenous protein demonstrated that RGGTA has a positive role in the maturation and anterograde trafficking of the β(2)AR, which requires the interaction of RGGTA with the β(2)AR L(339)L(340) motif. Furthermore, the β(2)AR modulates the geranylgeranylation of Rab6a, Rab8a, and Rab11a, but not of other Rab proteins tested in this study. Regulation of Rab geranylgeranylation by the β(2)AR was dependent on the RGGTA-interacting L(339)L(340) motif. Interestingly, a RGGTA-Y107F mutant was unable to regulate Rab geranylgeranylation but still promoted β(2)AR maturation, suggesting that RGGTA may have functions independent of Rab geranylgeranylation. We demonstrate for the first time an interaction between a transmembrane receptor and RGGTA which regulates the maturation and anterograde transport of the receptor, as well as geranylgeranylation of Rab GTPases.
authors: Service de Rhumatologie, Département de Médecine, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, the Centre de Recherche Clinique Étienne-Le Bel, and the Institut de Pharmacologie de Sherbrooke, Sherbrooke, Québec, Canada J1H 5N4.
authors: Véronik
authors: V
authors: Lachance
authors: Andréane
authors: A
authors: Cartier
authors: Samuel
authors: S
authors: Génier
authors: Sandra
authors: S
authors: Munger
authors: Pascale
authors: P
authors: Germain
authors: Pascale
authors: P
authors: Labrecque
authors: Jean-Luc
authors: JL
authors: Parent
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D011485:Protein Binding; D017368:Protein Prenylation; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D018343:Receptors, Adrenergic, beta-2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity; D020691:rab GTP-Binding Proteins / Q000378:metabolism
chemical_list: D018343:Receptors, Adrenergic, beta-2; D019883:Alkyl and Aryl Transferases; C075607:Rab geranylgeranyltransferase; D020691:rab GTP-Binding Proteins