Molecular basis of regulation of nerve function by glycosylation
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 |
Section | 一般 |
Research Field |
Biological pharmacy
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Research Institution | Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology |
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 |
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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Report
(4 results)
Research Products
(65 results)
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[Journal Article] Mutations in POMGNT1 cause non-syndromic retinitis pigmentosa.2016
Author(s)
Mingchu Xu, Takeyuki Yamada, Zixi Sun, Aiden Eblimit, Irma Lopez, Feng Wang, Hiroshi Manya, Shan Xu, Li Zhao, Yumei Li, Adva Kimchi, Dror Sharon, Ruifang Sui, Tamao Endo, Robert K. Koenekoop, Rui Chen
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Journal Title
Hum. Mol. Genet.
Volume: 25
Issue: 8
Pages: 1479-1488
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Identification of a post-translational modification with ribitol-phosphate and its defect in muscular dystrophy2016
Author(s)
Kanagawa M, Kobayashi K, Tajiri M, Manya H, Kuga A, Yamaguchi Y, Akasaka-Manya K, Furukawa J, Mizuno M, Kawakami H, Shinohara Y, Wada Y, Endo T, Toda T.
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Journal Title
Cell Reports
Volume: 14
Issue: 9
Pages: 2209-2223
DOI
NAID
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Japan as the front-runner of super aging societies: Perspectives from medicine and medical care in Japan.2015
Author(s)
Arai, H., Toba, K., Ouchi, Y., Endo, T., Shimokado, K., Tsubota, K., Matsuo, S., Mori, H., Yumura, K., Yokode, M., Rakugi, H., Ohshima, S.
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Journal Title
Geriatr. Gerontol. Int.
Volume: 15
Issue: 6
Pages: 673-687
DOI
Related Report
Peer Reviewed
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[Journal Article] POMGNT1 Is Glycosylated by Mucin-Type <i>O</i>-Glycans2015
Author(s)
Xin X, Akasaka-Manya K, Manya H, Furukawa J, Kuwahara N, Okada K, Tsumoto H, Higashi N, Kato R, Shinohara Y, Irimura T, Endo T.
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Journal Title
Biological and Pharmaceutical Bulletin
Volume: 38
Issue: 9
Pages: 1389-1394
DOI
NAID
ISSN
0918-6158, 1347-5215
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Change in N-glycosylation of plasma proteins in semisupercentenarians.2015
Author(s)
Miura, Y., Hashii, N., Tsumoto, H., Takakura, D., Ohta, Y., Abe, Y., Arai, Y., Kawasaki, N., Hirose, N., and Endo, T.
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Journal Title
PLoS One
Volume: 10
Issue: 11
Pages: e0142645-e0142645
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Human ISPD is a cytidyltransferase required for dystroglycan O-mannosylation.2015
Author(s)
Moniek Riemersma, D. Sean Froese, Walinka van Tol, Udo F. Engelke, Jolanta Kopec, Monique van Scherpenzeel, Angel Ashikov, Tobias Krojer4, Frank von Delft, Marco Tessari, Anna Buczkowska, Ewa Swiezewska, Lucas T. Jae, Thijn R. Brummelkamp, Hiroshi Manya, Tamao Endo, Hans van Bokhoven, Wyatt W. Yue, Dirk J. Lefeber
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Journal Title
Chem. Biol.
Volume: 22
Issue: 12
Pages: 1643-1652
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Structural and biochemical characterization of O-mannose-linked HNK-1 glycan expressed on phosphacan in developing mouse brains.2014
Author(s)
Morise J, Kizuka Y, Yabuno K, Tonoyama Y, Hashii N, Kawasaki N, Manya H, Miyagoe-Suzuki Y, Takeda S, Endo T, Maeda N, Takematsu H, and Oka S.
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Journal Title
Glycobiology
Volume: 24
Issue: 3
Pages: 314-324
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Novel POMGnT1 mutations cause muscle-eye-brain disease in Chinese patients2013
Author(s)
Jiao H, Manya H, Wang S, Zhang Y, Li X, Xiao J, Yang Y, Kobayashi K, Toda T, Endo T, Wu X, Xiong H.
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Journal Title
Mol Genet Genomics
Volume: 288
Issue: 7-8
Pages: 297-308
DOI
Related Report
Peer Reviewed
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[Presentation] isecting GlcNAc on BACE1 is a novel therapeutic target for Alzheimer’s disease2015
Author(s)
Kizuka, Y., Kitazume, S., Nakano, M., Saido, T. C., Hashimoto, Y., Endo, T., Taniguchi, N.
Organizer
23rd International Symposium on Glycoconjugates (GLYCO23)
Place of Presentation
Split (Croatia)
Year and Date
2015-09-15
Related Report
Int'l Joint Research
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[Presentation] Analysis of protein O-mannosyltransferase complex formation in the endoplasmic reticulum.2014
Author(s)
Endo, T., Yamada, T., Takahashi, T., Akasaka-Manya, K., Manya, H.
Organizer
9th International Symposium on Glycosyltransferases (Glyco-T 2014)
Place of Presentation
Porto, Portugal
Year and Date
2014-06-18 – 2014-06-21
Related Report
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