Tissue Specificity of CFTR Trafficking

The cystic fibrosis transmembrane conductance regulator (CFTR) belongs to the family of ATP binding cassette (ABC) transporters, but forms a cAMP-activated Cl- channel that medi-ates transepithelial Cl- secretion in various fluid-transporting epithelia.1-3 CFTR is mutated in patients with cystic fibrosis (CF). In the airway, CFTR plays an essential role in maintaining mucociliary clearance by regulating the airway surface liquid.4,5 A central aspect of this regulation involves control of Cl- secretion across polarized epithelial cells, which is modulated at the level of both CFTR channel activity and cell membrane abundance (reviewed in6,7). The plasma membrane abundance of CFTR in turn depends on its biosynthetic processing and post-matu-rational trafficking (reviewed in8). The long plasma membrane stability of CFTR stands in contrast to its inefficient biosynthetic processing and primarily reflects efficient recycling, which i