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Vol. 16, Issue 12, 5572-5578, December 2005

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Assembly-dependent Surface Targeting of the Heterodimeric GABA_B Receptor Is Controlled by COPI but Not 14-3-3

Carsten Brock ^*    ||, Laure Boudier ^*    ||, Damien Maurel ^*    ||, Jaroslav Blahos ^{*    || ¶}, and Jean-Philippe Pin ^*    ||

^* CNRS UMR5203, Montpellier F-34094 France; INSERM U661, Montpellier F-34094 France; University of Montpellier I, Montpellier F-34094 France; University of Montpellier II, Montpellier F-34094 France; and ^|| Département de Pharmacologie Moléculaire, Institut de Génomique Fonctionnelle, Montpellier F-34094 Cedex 5, France

Submitted May 6, 2005; Revised September 8, 2005; Accepted September 12, 2005
Monitoring Editor: Akihiko Nakano

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 GABA_B 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 GABA_B 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.

Abbreviations used: CC, coiled coil; COPI, coat protein I complex; GABA, -aminobutyric acid, GB1/2, GABA type B receptor 1/2; GPCR, G protein-coupled receptor; HEK, human embryonic kidney.

^¶ Present address: Department of Molecular Pharmacology, Institute of Experimental Medicine, Academie of Science of the Czech Republic, Videnska 1083, 142 20 Prague 4, Czech Republic.

Address correspondence to: J.-P. Pin (jppin{at}igf.cnrs.fr) or C. Brock (cbrock{at}igf.cnrs.fr).

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