THE CYSTIC-FIBROSIS MUTATION (DELTA-F508) DOES NOT INFLUENCE THE CHLORIDE CHANNEL ACTIVITY OF CFTR

The cystic fibrosis transmembrane conductance regulator (CFTR) is a phosphorylation-regulated Cl- channel. In most mammalian cells, the functional consequences of the most common CF mutation, DELTAF508-CFTR, cannot be assessed as the mutant protein undergoes biosynthetic arrest. However, function can be studied in the baculovirus-insect cell expression system where DELTAF508-CFTR does not appear to undergo such arrest. Our results show that phosphorylation-regulated Cl- channel activity of DELTAF508-CFTR is similar to that of wild-type CFTR. This observation was confirmed in comparative studies of purified DELTAF508-CFTR and CFTR reconstituted in planar lipid bilayers. Therefore, we suggest that this common mutation does not result in a significant alteration in CFTR function.