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Effects of Single Genetic Damage in Carbohydrate‐Recognizing Proteins in Mouse Serum N ‐Glycan Profile Revealed by Simple Glycotyping Analysis
Author(s) -
Amano Maho,
Hashimoto Ryo,
Nishimura ShinIchiro
Publication year - 2012
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201100595
Subject(s) - glycan , glycosylation , biology , glycosyltransferase , galectin , glycome , lectin , receptor , biochemistry , glycoprotein , microbiology and biotechnology , gene
Gene knock‐out of C ‐type lectin receptors expressed in dendritic cells induced significant alteration of serum N ‐glycans compared with that of gender‐matched controls. Glycotyping analysis suggested that putative‐core fucosylation is strongly influenced by differences in the dominant mechanisms after carbohydrate recognition by pattern‐recognition receptors, endocytosis of ligands, or induction of cytokines/chemokines. However, the loss of galectin‐9, a ligand for T‐helper type 1‐specific cell‐surface molecule, did not affect most N ‐glycan profiles. Interestingly, lack of the Chst3 gene (chondroitin 6‐sulfotransferase) appeared to influence markedly the expression of most N ‐glycans, especially highly modified glycoforms bearing multiple Neu5Gc, Fuc, and LacNAc units. In contrast, genetic mutations in B4galnt1 and B4galnt2 (GalNAc transferase, responsible for the synthesis of many gangliosides) induced no discernable alteration. These results indicate that the biosynthesis of N ‐glycans of serum glycoproteins can be affected not only by direct genetic mutations in the glycosyltransferases but also by changes in metabolite availability in sugar nucleotide synthesis and Golgi N ‐glycosylation pathways caused concertedly in whole cells, tissues, and organs by milder deficiencies in immune cell‐surface lectins. Many common chronic conditions, such as autoimmunity, metabolic syndrome, and aging/dementia result.