Endosomal SNARE proteins regulate CFTR activity and trafficking in epithelial cells. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Experimental Cell Research Année : 2008

Endosomal SNARE proteins regulate CFTR activity and trafficking in epithelial cells.

Résumé

The Cystic Fibrosis Transmembrane conductance Regulator (CFTR) protein is a chloride channel localized at the apical plasma membrane of epithelial cells. We previously described that syntaxin 8, an endosomal SNARE (Soluble N-ethylmaleimide-sensitive factor Attachment protein REceptor) protein, interacts with CFTR and regulates its trafficking to the plasma membrane and hence its channel activity. Syntaxin 8 belongs to the endosomal SNARE complex which also contains syntaxin 7, vti1b and VAMP8. Here, we report that these four endosomal SNARE proteins physically and functionally interact with CFTR. In LLC-PK1 cells transfected with CFTR and in Caco-2 cells endogenously expressing CFTR, we demonstrated that endosomal SNARE protein overexpression inhibits CFTR activity but not swelling- or calcium-activated iodide efflux, indicating a specific effect upon CFTR activity. Moreover, co-immunoprecipitation experiments in LLC-PK1-CFTR cells showed that CFTR and SNARE proteins belong to a same complex and pull-down assays showed that VAMP8 and vti1b preferentially interact with CFTR N-terminus tail. By cell surface biotinylation and immunofluorescence experiments, we evidenced that endosomal SNARE overexpression disturbs CFTR apical targeting. Finally, we found a colocalization of CFTR and endosomal SNARE proteins in Rab11-positive recycling endosomes, suggesting a new role for endosomal SNARE proteins in CFTR trafficking in epithelial cells.

Dates et versions

hal-00399077 , version 1 (25-06-2009)

Identifiants

Citer

Frédéric Bilan, Magali Nacfer, Fleur Fresquet, Caroline Norez, Patricia Melin, et al.. Endosomal SNARE proteins regulate CFTR activity and trafficking in epithelial cells.. Experimental Cell Research, 2008, 314 (11-12), pp.2199-2211. ⟨10.1016/j.yexcr.2008.04.012⟩. ⟨hal-00399077⟩
229 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More