Journal Article

Core fucosylation of N-linked glycans in leukocyte adhesion deficiency/congenital disorder of glycosylation IIc fibroblasts

Laura Sturla, Floriana Fruscione, Katsuhisa Noda, Eiji Miyoshi, Naoyuki Taniguchi, Paola Contini and Michela Tonetti

in Glycobiology

Published on behalf of Society for Glycobiology

Volume 15, issue 10, pages 924-934
Published in print October 2005 | ISSN: 0959-6658
Published online May 2005 | e-ISSN: 1460-2423 | DOI:
Core fucosylation of N-linked glycans in leukocyte adhesion deficiency/congenital disorder of glycosylation IIc fibroblasts

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Leukocyte adhesion deficiency/congenital disorder of glycosylation IIc (LAD II/CDG IIc) is a genetic disease characterized by a decreased expression of fucose in glycoconjugates, resulting in leukocyte adhesion deficiency and severe morphological and neurological abnormalities. The biochemical defect is a reduced transport of guanosine diphosphate-L-fucose (GDP-L-fucose) from cytosol into the Golgi compartment, which reduces its availability as substrate for fucosyltransferases. The aim of this study was to determine the effects of a limited supply of GDP-L-fucose inside the Golgi on core fucosylation (a1,6-fucose linked to core N-acetylglucosamine [GlcNAc]) of N-linked glycans in LAD II fibroblasts. The results showed that, although [3H]fucose incorporation was generally reduced in LAD II cells, core fucosylation was affected to a greater extent compared with other types of fucosylation of N-linked oligosaccharides. In particular, core fucosylation was found to be nearly absent in biantennary negatively charged oligosaccharides, whereas other types of structures, in particular triantennary neutral species, were less affected by the reduction. Expression and activity of a1,6-fucosyltransferase (FUT8) in control and LAD II fibroblasts were comparable, thus excluding the possibility of a decreased activity of the transferase. The data obtained confirm that the concentration of GDP-L-fucose inside the Golgi can differentially affect the various types of fucosylation in vivo and also indicate that core fucosylation is not dependent only on the availability of GDP-L-fucose, but it is significantly influenced by the type of oligosaccharide structure. The relevant reduction in core fucosylation observed in some species of oligosaccharides could also provide clues for the identification of glycans involved in the severe developmental abnormalities observed in LAD II.

Keywords: congenital disorder of glycosylation; fibroblasts; fucose; leukocytes adhesion deficiency; α1,6-fucosyltransferase; BSA, bovine serum albumin; Con A, Canavalia ensiformis lectin; ECL, enhanced chemiluminescence; endo F3, endoglycosidase F3; endo H, endoglycosidase H; FUT8, α1,6-fucosyltransferase; GDP-L-fucose, guanosine diphosphate-L-fucose; GlcNAc, N-acetylglucosamine; HRD, horseradish peroxidase; LAD II/CDG IIc, leukocyte adhesion deficiency type II/congenital defect of glycosylation IIc; LCA, Lens culinaris agglutinin; PBS, phosphate buffered saline; PNGase F, Peptide N-glycanase F; TBS, tris buffered saline

Journal Article.  7730 words.  Illustrated.

Subjects: Carbohydrates

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