Assembly-dependent surface targeting of the heterodimeric GABAB Receptor is controlled by COPI but not 14-3-3.

Carsten Brock (1) , Laure Boudier (1) , Damien Maurel (1, 2) , Jaroslav Blahos (1) , Jean-Philippe Pin (1, 3)

1 IGF - Institut de Génomique Fonctionnelle
2 HTRF - Homogeneous Time-resolved Fluorescence
3 Département de Pharmacologie Moléculaire

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.

Mots clés: GPCR; surface trafficking; COP1; GABAB

Domaines: Neurobiologie; Pharmacologie; Organisation et fonctions cellulaires [q-bio.SC]

Carsten Brock, Laure Boudier, Damien Maurel, Jaroslav Blahos, Jean-Philippe Pin. Assembly-dependent surface targeting of the heterodimeric GABAB Receptor is controlled by COPI but not 14-3-3.. Molecular Biology of the Cell, 2005, 16 (12), pp.5572-8. ⟨10.1091/mbc.E05-05-0400⟩. ⟨hal-00318967v2⟩