Kazuhisa Yoshitake

Calnexin Δ185–520 partially reverses the misprocessing of the ΔF508 cystic fibrosis transmembrane conductance regulator1

Abnormal retention of ΔF508 CFTR (cystic fibrosis transmembrane conductance regulator) in the endoplasmic reticulum is a major cause of cystic fibrosis (CF). We show that calnexin Δ185–520 but not calnexin can partially reverse the mislocalization of ΔF508 CFTR. This 256‐amino acid protein has neither the transmembrane domain nor the P domain of calnexin. Calnexin Δ185–520 interacted with CFTR directly, and was secreted into the extracellular compartment over time. Forty‐eight hours after transfection into CHO cells, calnexin Δ185–520 increased the conversion of immature ΔF508 CFTR into mature ΔF508 CFTR. In immortalized human CF cell lines expressing ΔF508 CFTR, a halide efflux assay showed that calnexin Δ185–520 partially restored CFTR function. These data indicate that calnexin Δ185–520 may give a clue to develop the therapeutic way of cystic fibrosis with ΔF508 CFTR.