Calnexin Δ185-520 partially reverses the misprocessing of the ΔF508 cystic fibrosis transmembrane conductance regulator

Abnormal retention of DeltaF508 CFTR (cystic fibrosis transmembrane conductance regulator) in the endoplasmic reticulum is a major cause of cystic fibrosis (CF). We show that calnexin Delta185-520 but not calnexin can partially reverse the mislocalization of DeltaF508 CFTR. This 256-amino acid protein has neither the transmembrane domain nor the P domain of calnexin. Calnexin Delta185-520 interacted with CFTR directly, and was secreted into the extracellular compartment over time. Forty-eight hours after transfection into CHO cells, calnexin Delta185-520 increased the conversion of immature DeltaF508 CFTR into mature DeltaF508 CFTR. In immortalized human CF cell lines expressing DeltaF508 CFTR, a halide efflux assay showed that calnexin Delta185-520 partially restored CFTR function. These data indicate that calnexin Delta185-520 may give a clue to develop the therapeutic way of cystic fibrosis with DeltaF508 CFTR. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.