Glycobiology Advance Access originally published online on May 25, 2005
Glycobiology 2005 15(10):924-934; doi:10.1093/glycob/cwi081
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Core fucosylation of N-linked glycans in leukocyte adhesion deficiency/congenital disorder of glycosylation IIc fibroblasts
2 Department of Experimental Medicine and Center of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV, 1, 16132, Genova, Italy; 3 Department of Biochemistry, Osaka University, Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan; and 4 Department of Internal Medicine, University of Genova, Viale Benedetto XV, 6, 16132, Genova, Italy
1 To whom correspondence should be addressed; e-mail: tonetti{at}unige.it
Received on December 28, 2004; revised on May 17, 2005; accepted on May 19, 2005
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.
Key words:
congenital disorder of glycosylation
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fibroblasts
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fucose
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leukocytes adhesion deficiency
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1,6-fucosyltransferase
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