| Project/Area Number |
25670140
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
General medical chemistry
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| Research Institution | Nagoya University |
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Principal Investigator |
Okajima Tetsuya 名古屋大学, 医学(系)研究科(研究院), 教授 (20420383)
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| Co-Investigator(Kenkyū-buntansha) |
KUROSAKA AKIRA 京都産業大学, 総合生命科学部, 教授 (90186536)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2013: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| Keywords | α-Dystroglycan / GTDC2 / CTD110.6 / zebrafish / ジストログリカン / 小胞体 / GlcNAc / トランスポーター / O-GlcNAc / EOGT / Dystroglycan |
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| Outline of Final Research Achievements |
Hypoglycosylation is a common characteristic of α-dystroglycanopathy, which is a group of congenital muscular dystrophies. More than ten genes, including GTDC2, have been implicated in α-dystroglycanopathies. In this study, we showed that GTDC2 generates CTD110.6 antibody-reactive N-acetylglucosamine (GlcNAc) epitopes on the α-dystroglycan (α-DG) within the mucin-like domain of α-DG in the endoplasmic reticulum. Mutations of GTDC2 identified in Walker-Warburg syndrome resulted in decreased glycosylation. Inactivation of GTDC2 function in zebrafish resulted in enlarged cerebral ventricle and microphthalmia, that is associated with dystroglycanopathy. Thus, GTDC2 is a novel glycosyltransferase catalyzing GlcNAcylation of α-DG in the endoplasmic reticulum. Zebrafish will serve as a suitable model organism to study GlcNAc modification of α-DG and to analyze defective O-glycosylation in α-dystroglycanopathies.
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