RRC ID 35676
著者 Yan S, Bleuler-Martinez S, Plaza DF, Künzler M, Aebi M, Joachim A, Razzazi-Fazeli E, Jantsch V, Geyer R, Wilson IB, Paschinger K.
タイトル Galactosylated fucose epitopes in nematodes: increased expression in a Caenorhabditis mutant associated with altered lectin sensitivity and occurrence in parasitic species.
ジャーナル J Biol Chem
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.
巻・号 287(34)
ページ 28276-90
公開日 2012-8-17
DOI 10.1074/jbc.M112.353128
PII S0021-9258(20)68368-5
PMID 22733825
PMC PMC3436517
MeSH 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*
IF 4.238
引用数 35
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
線虫 hex-2 and hex-3 mutants (tm2350 and tm2725)