| Co-Investigator(Kenkyū-buntansha) |
NAGAI-DENDA Kaori The University of Tokyo, Graduate school of Pharmaceutical Sciences, Research Associate, 大学院・薬学系研究科, 助手 (00313122)
TSUIJI Makoto The University of Tokyo, Graduate school of Pharmaceutical Sciences, Research Associate, 大学院・薬学系研究科, 助手 (90302611)
HIGASHI Nubuaki The University of Tokyo, Graduate school of Pharmaceutical Sciences, Lecturer, 大学院・薬学系研究科, 講師 (40302616)
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| Research Abstract |
The specific aim of this proposal was to prove or disprove a hypothesis whether mucins, epithelial surface glycoproteins with a high degree of O-glycosylation, played roles as specific defense molecules against parasites, such as protozoa, bacteria, and viruses. The following conclusions were obtained.
(1)Epithelial mucins were highly diverse in their glycosylation profiles.
(2)The specific glycosylation of mucins were regulated in a high degree of fidelity by concerted actions of multiple UDP-GalNAc-polypeptide N-acetylgalactosaminyltransferases (ppGalNAc Ts).
(3)A Th2 cytokine, IL-4, drastically enhance the expression of a few ppGalNAc Ts (ppGalNAc T1, 4, and 7), which resulted in an alteration of glycosylation profiles of mucin 2.
(4)After such alterations, the secreted mucins changed its reactivity with lectins, carbohydrate-binding proteins.
(5)Various oligosaccharide-polypeptide complexes were prepared by the use of recombinant ppGalNAc Ts and other glycosyltransferases in vitro. They were tested to determine the specificity of lectins toward mucin motifs.
(6)Variations in mucin motifs on pathogens, such as the surface coat glycoproteins of Ebola virus, were also shown to play important roles in the regulation of infective processes.
(7)In these processes, C-type/galactose-type lectins on macrophages and dendritic cells were shown to be significantly involved.
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