Mc. Glick et al., Activity of fucosyltransferases and altered glycosylation in cystic fibrosis airway epithelial cells, BIOCHIMIE, 83(8), 2001, pp. 743-747
Cystic fibrosis (CF) glycoconjugates have a glycosylation phenotype of incr
eased fucosylation and/or decreased sialylation when compared with non-CF.
A major increase in fucosyl residues linked alpha1,3 to antennary GlcNAc wa
s observed when surface membrane glycoproteins of CF airway epithelial cell
s were compared to those of non-CF airway cells. Importantly, the increase
in the fucosyl residues was reversed with transfection of CF cells with wil
d type CFTR cDNA under conditions which brought about a functional correcti
on of the Cl- channel defect in the CF cells. In contrast, examination of f
ucosyl residues in alpha1,2 linkage by a specific alpha1,2 fucosidase showe
d that cell surface glycoproteins of the non-CF cells had a higher percenta
ge 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 w
ere compared. In striking contrast, the enzyme activity and the mRNA of alp
ha1,2 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 glyc
oproteins encounter alpha1,3FucT before either the sialyl- or alpha1,2 fuco
syltransferases. In subsequent compartments, little or no terminal glycosyl
ation 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 th
e CF glycophenotype. (C) 2001 Societe francaise de biochimie et biologie mo
leculaire/Editions scientifiques et medicales Elsevier SAS. All rights rese
rved.