Galactosylated fucose epitopes in nematodes: increased expression in a Caenorhabditis mutant associated with altered lectin sensitivity and occurrence in parasitic species.
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.
Department für Chemie, Universität für Bodenkultur, A-1190 Wien, Austria.
Shi
S
Yan
Silvia
S
Bleuler-Martinez
David Fernando
DF
Plaza
Markus
M
Künzler
Markus
M
Aebi
Anja
A
Joachim
Ebrahim
E
Razzazi-Fazeli
Verena
V
Jantsch
Rudolf
R
Geyer
Iain B H
IB
Wilson
Katharina
K
Paschinger
D000117:Acetylglucosamine / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology; D017165:Ascaris suum / Q000235:genetics / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D015195:Drug Design; D000939:Epitopes / Q000235:genetics / Q000378:metabolism*; D005643:Fucose / Q000235:genetics / Q000378:metabolism*; D037501:Galectin 2 / Q000494:pharmacology; D006031:Glycosylation; D006596:Hexosaminidases / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009815:Oesophagostomum / Q000235:genetics / Q000378:metabolism; D011134:Polysaccharides / Q000235:genetics / Q000378:metabolism*
D000871:Anthelmintics; D029742:Caenorhabditis elegans Proteins; D000939:Epitopes; D037501:Galectin 2; D011134:Polysaccharides; D005643:Fucose; D006596:Hexosaminidases; D000117:Acetylglucosamine