Immunocytochemical analysis reveals differences between the subcellular localization of normal and ΔPhe508 recombinant cystic fibrosis transmembrane conductance regulator

Cystic fibrosis (CF) is caused by mutations in the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR). The most common mutation responsible for CF is the deletion of amino acid residue Phe508, with an average allelic frequency of 70%. We have isolated an anti-CFTR monoclonal antibody which specifically recognizes recombinant normal and ΔPhe508-CFTR produced by a vaccinia virus expression system. Immunocytochemical analysis of L cells expressing either normal or ΔPhe508-CFTR showed a marked difference in subcellular distribution. Normal CFTR had a distinct localization in the perinuclear area and was also associated with the plasma membrane. ΔPhe508-CFTR essentially lacked the membrane-associated distribution and was present throughout the cytoplasm. This heterologous expression system thus provides a model system for studying the subcellular localization of different mutant forms of CFTR.