Processing and intracellular trafficking of wild-type and mutant CFTR

The cellular quality control, involving molecular chaperones, causes substantial retention of F508del-CFTR in the endoplasmic reticulum (ER). We overexpresscd the Hsp70 chaperone in vivo and observed no changes in degradation rate of the core-glycosylated form, nor in the maturation efficiency, for either wt- or F508del-CFTR. Co-transfection with co-chaperone Hdj-1/Hsp40, however, stabilizes immature wt-CFTR, but not F508del-CFTR, suggesting that these chaperones act on a wt-specific conformation. As no increased maturation efficiency occurs, the lack of these two chaperones does not seem to be critical for ER retention. 4-phenylbutyrate and deoxyspergualin, previously described to interfere with Hsp70 binding, were also tested, but only destabilization of F508del-CFTR was observed.