title: Assembly-dependent surface targeting of the heterodimeric GABAB Receptor is controlled by COPI but not 14-3-3.
abstract: Cell surface expression of transmembrane proteins is strictly regulated. Mutually exclusive interaction with COPI or 14-3-3 proteins has been proposed as a mechanism underlying such trafficking control of various proteins. In particular, 14-3-3 dimers have been proposed to "sense" correctly assembled oligomers, allowing their surface targeting by preventing COPI-mediated intracellular retention. Here we examined whether such a mechanism is involved in the quality control of the heterodimeric G protein-coupled GABAB receptor. Its GB1 subunit, carrying the retention signal RSR, only reaches the cell surface when associated with the GB2 subunit. We show that COPI and 14-3-3 specifically bind to the GB1 RSR sequence and that COPI is involved in its intracellular retention. However, we demonstrate that the interaction with 14-3-3 is not required for proper function of the GABAB receptor quality control. Accordingly, competition between 14-3-3 and COPI cannot be considered as a general trafficking control mechanism. A possible other role for competition between COPI and 14-3-3 binding is discussed.
authors.affiliation: CNRS UMR5203, Montpellier F-34094 France.
authors.forename: Carsten
authors.initials: C
authors.lastname: Brock
authors.forename: Laure
authors.initials: L
authors.lastname: Boudier
authors.forename: Damien
authors.initials: D
authors.lastname: Maurel
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Blahos
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Pin
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism*; D001692:Biological Transport; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology*; D003001:Cloning, Molecular; D020755:Coat Protein Complex I / Q000378:metabolism*; D019281:Dimerization; D006801:Humans; D007668:Kidney; D007700:Kinetics; D018613:Microscopy, Confocal; D016133:Polymerase Chain Reaction; D018080:Receptors, GABA-B / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014162:Transfection
chemical_list: D048948:14-3-3 Proteins; D020755:Coat Protein Complex I; D018080:Receptors, GABA-B