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Glycobiology

Year: 2010  |  Volume: 20  |  Issue: 11  |  Page No.: 1353 - 1365

Neural-specific {alpha}3-fucosylation of N-linked glycans in the Drosophila embryo requires Fucosyltransferase A and influences developmental signaling associated with O-glycosylation

D Rendic, M Sharrow, T Katoh, B Overcarsh, K Nguyen, J Kapurch, K Aoki, I. B. H Wilson and M. Tiemeyer

Abstract

Addition of fucose (Fuc) to glycoprotein N-linked glycans or in O-linkage directly to Ser/Thr residues modulates specific cell–cell interactions and cell signaling events. Vertebrates and invertebrates add Fuc in 6-linkage to the reducing terminal N-acetylglucosamine residue of N-glycans. In Drosophila and other invertebrates, Fuc can also be added in 3-linkage to the same residue. These difucosylated N-glycans are recognized by anti-horseradish peroxidase (anti-HRP) antisera, providing a well-established marker for insect neural tissue. To understand the mechanisms and consequences of tissue-specific glycan expression, we identified a single 3-fucosyltransferase (FucTA) that produces the anti-HRP epitope in Drosophila embryos. FucTA transcripts are temporally and spatially restricted to cells that express the anti-HRP epitope and are missing in a mutant that lacks neural 3-fucosylation. Transgenic expression of FucTA, but not of any other candidate 3-fucosyltransferase, rescues the anti-HRP epitope in the embryonic nervous system of this mutant. Mass spectrometric characterization of the N-glycans of Drosophila embryos overexpressing FucTA confirms that this enzyme is indeed responsible for the biosynthesis of difucosylated glycans in vivo. Whereas ectopic expression of FucTA in the larval wing disc produces mild wing notching, the heterochronic, pan-neural expression of FucTA in early differentiating neurons generates neurogenic and cell migration phenotypes; this latter effect is associated with reduced GDP-Fuc levels in the embryo and indicates that the diversion of fucosylation resources towards fucosylation of N-glycans has an impact on developmental signaling associated with O-fucosylation.

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