Activity of fucosyltransferases and altered glycosylation in cystic fibrosis airway epithelial cells

Cystic fibrosis (CF) glycoconjugates have a glycosylation phenotype of increased fucosylation and/or decreased sialylation when compared with non-CF. A major increase in fucosyl residues linked alpha1,3 to antennary GlcNAc was observed when surface membrane glycoproteins of CF airway epithelial cells were compared to those of non-CF airway cells. Importantly, the increase in the fucosyl residues was reversed with transfection of CF cells with wild type CFTR cDNA under conditions which brought about a functional correction of the Cl- channel defect in the CF cells. In contrast, examination of fucosyl residues in alpha1,2 linkage by a specific alpha1,2 fucosidase showed that cell surface glycoproteins of the non-CF cells had a higher percentage of fucose in alpha1,2 linkage than the CF cells. Airway epithelial cells in primary culture had a similar reciprocal relationship of alpha1,2- and alpha1,3-fucosylation when CF and non-CF surface membrane glycoconjugates were compared. In striking contrast, the enzyme activity and the mRNA of alpha1,2 fucosyltransferase did not reflect the difference in glycoconjugates observed between the CF and non-CF cells. We hypothesize that mutated CFTR may cause faulty compartmentalization in the Golgi so that the nascent glycoproteins encounter alpha1,3FucT before either the sialyl- or alpha1,2 fucosyltransferases. In subsequent compartments, little or no terminal glycosylation can take place since the sialyl- or alpha1,2 fucosyltransferases are unable to utilize a substrate, which is facosylated in alpha1,3 position on antennary GlcNAc. This hypothesis, if proven correct, could account for the CF glycophenotype. (C) 2001 Societe francaise de biochimie et biologie moleculaire/Editions scientifiques et medicales Elsevier SAS. All rights reserved.