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Publikationstyp: Zeitschriftenaufsatz
Dokumentart: Originalarbeit

Publikationsjahr: 2012

AutorInnen: Yan, S; Bleuler-Martinez, S; Plaza, DF; Künzler, M; Aebi, M; Joachim, A; Razzazi-Fazeli, E; Jantsch, V; Geyer, R; Wilson, IB; Paschinger, K

Titel: Galactosylated fucose epitopes in nematodes: increased expression in a Caenorhabditis mutant associated with altered lectin sensitivity and occurrence in parasitic species.

Quelle: J Biol Chem. 2012; 287(34):28276-28290



Autor/innen der Vetmeduni Vienna:

Joachim Anja
Razzazi-Fazeli Ebrahim
Yan Shi

Beteiligte Vetmed-Organisationseinheiten
Institut für Parasitologie
VetCore


Abstract:
The modification of α1,6-linked fucose residues attached to the proximal (reducing-terminal) core N-acetylglucosamine residue of N-glycans by β1,4-linked galactose ("GalFuc" epitope) is a feature of a number of invertebrate species including the model nematode Caenorhabditis elegans. A pre-requisite for both core α1,6-fucosylation and β1,4-galactosylation is the presence of a nonreducing terminal N-acetylglucosamine; however, this residue is normally absent from the final glycan structure in invertebrates due to the action of specific hexosaminidases. Previously, we have identified two hexosaminidases (HEX-2 and HEX-3) in C. elegans, which process N-glycans. In the present study, we have prepared a hex-2;hex-3 double mutant, which possesses a radically altered N-glycomic profile. Whereas in the double mutant core α1,3-fucosylation of the proximal N-acetylglucosamine was abolished, the degree of galactosylation of core α1,6-fucose increased, and a novel Galα1,2Fucα1,3 moiety attached to the distal core N-acetylglucosamine residue was detected. Both galactosylated fucose moieties were also found in two parasitic nematodes, Ascaris suum and Oesophagostomum dentatum. As core modifications of N-glycans are known targets for fungal nematotoxic lectins, the sensitivity of the C. elegans double hexosaminidase mutant was assessed. Although this mutant displayed hypersensitivity to the GalFuc-binding lectin CGL2 and the N-acetylglucosamine-binding lectin XCL, the mutant was resistant to CCL2, which binds core α1,3-fucose. Thus, the use of C. elegans mutants aids the identification of novel N-glycan modifications and the definition of in vivo specificities of nematotoxic lectins with potential as anthelmintic agents.

Keywords Pubmed: Acetylglucosamine/genetics
Acetylglucosamine/metabolism
Animals
Anthelmintics/pharmacology
Ascaris suum/genetics
Ascaris suum/metabolism
Caenorhabditis elegans/genetics
Caenorhabditis elegans/metabolism*
Caenorhabditis elegans Proteins/genetics
Caenorhabditis elegans Proteins/metabolism*
Drug Design
Epitopes/genetics
Epitopes/metabolism*
Fucose/genetics
Fucose/metabolism*
Galectin 2/pharmacology
Glycosylation
Hexosaminidases/genetics
Hexosaminidases/metabolism*
Mutation
Oesophagostomum/genetics
Oesophagostomum/metabolism
Polysaccharides/genetics
Polysaccharides/metabolism*


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