Functional analysis of orphan glycolsyltransferases associated with congenital muscular dystrophies using model organisms
| 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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Report
(4 results)
Research Products
(21 results)
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[Journal Article] Post-weaning increases in the milk-fat globule EGF-factor VIII on fat globules in mouse milk and in the uptake of the fat globules by HC11 mammary epithelial cells.2013
Author(s)
Nakatani, H., Yasueda, T., Oshima, K., Okajima, T., Nadano, D., Flint, D. J., and Matsuda, T.
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Journal Title
J Biochem
Volume: 153
Issue: 1
Pages: 31-41
DOI
Related Report
Peer Reviewed
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[Journal Article] Dephosphorylation reduces passage of ovalbumin antigen through intestinal epithelial Caco-2 cell monolayers.2013
Author(s)
Matsubara, T., Akiyama, Y., Oshima, K., Okajima, T., Nadano, D., and Matsuda, T.
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Journal Title
J Biochem
Volume: 153
Issue: 4
Pages: 347-354
DOI
Related Report
Peer Reviewed
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[Book] ST6 N-acetylgalactosaminide alpha-2,6-sialyltransferase 5,6 (ST6GALNAC5,6) in “Handbook of Glycosyltransferases and Related Genes” (Eds. Taniguchi, N., Honke, K., Fukuda, M., Narimatsu, H., Yamaguchi, Y., Angata, T.)2013
Author(s)
Furukawa K, Okajima, T. Tsuchida A, and Furukawa, K.
Total Pages
1707
Publisher
Springer
Related Report
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[Book] ST3 beta-galactoside alpha-2,3-sialyltransferase 6 (ST3GAL6). in “Handbook of Glycosyltransferases and Related Genes” (Eds. Taniguchi, N., Honke, K., Fukuda, M., Narimatsu, H., Yamaguchi, Y., Angata, T.)2013
