| Project/Area Number |
25293016
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology |
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Principal Investigator |
Endo Tamao 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 副所長 (30168827)
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| Co-Investigator(Renkei-kenkyūsha) |
Masami Miura 地方独立行政法人 東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 専門副部長 (40291091)
Miura Yuri 地方独立行政法人 東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究副部長 (00216574)
Keiko Manya 地方独立行政法人 東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (70415496)
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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 |
¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
Fiscal Year 2015: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2014: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2013: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
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| Keywords | 糖鎖 / 筋ジストロフィー / O-マンノース / 糖転移酵素 / 脳の発生 |
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| Outline of Final Research Achievements |
α-Dystroglycanopathy is a type of congenital muscular dystrophies with neurological abnormality. Defect of O-mannosyl glycan on α-dystroglycan is a primary cause of α-dystroglycanopathy. In this study, we elucidated the precise structure of O-mannosyl glycan that contains ribitol 5-phosphate (Rbo5P); [GlcA-Xyl]n-Rbo5P-1Rbo5P-3GalNAcβ1-3GlcNAcβ1-4(phospho-6)Man. Rbo5P forms a tandem repeat and functions as a scaffold for the formation of the ligand-binding moiety. We also revealed that three α-dystroglycanopathy-causing proteins with unknown function, fukutin (Fukuyama Congenital Muscular Dystrophy), FKRP (Limb Girdle Muscular Dystrophy) and ISPD (Walker-Warburg syndrome), are involved in the synthesis of tandem Rbo5P. Fukutin and FKRP are Rbo5P transferases and ISPD synthesizes CDP-Rbo. We reported a novel O-mannosyl glycan structure and provided new insight into the molecular basis of its biosynthetic pathway and its role in nerve function in the brain.
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