DYSFUNCTION OF CFTR BEARING THE DELTA-F508 MUTATION

The cystic fibrosis transmembrane conductance regulator (CFTR) is muta ted in patients with cystic fibrosis (CF). The most common CF-associat ed mutation is deletion of phenylanine at residue 508, CFTR triangle F 508. When expressed in heterologous cells, CFTR bearing the triangle F 508 mutation fails to progress through the normal biosynthetic pathway and fails to traffic to the plasma membrane. As a result, CFTR triang le F508 is mislocalized and not present in the apical membrane of prim ary cultures of airway epithelia. Consequently, the apical membrane of CF airway epithelia is Cl--impermeable, a defect that probably contri butes to the pathogenesis of the disease.