Biosynthetic pathway of O-mannosyl glycan
Project/Area Number |
16K08262
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | 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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Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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Keywords | 糖鎖 / O-マンノース / 筋ジストロフィー / 糖転移酵素 |
Outline of Final Research Achievements |
Abnormalities in O-mannosyl glycan cause a group of congenital muscular dystrophies known as dystroglycanopathies. We have identified complete structure of core M3 O-mannosyl glycan. It is a novel structure in mammals containing a newly identified glycan component, ribitol-5-phosphate. In this study, I revealed functions of gene products responsible for dystroglycanopathy, POMGNT1, FKTN, FKRP, and TMEM5. The results are significant findings related to investigation of comprehensive understanding of biosynthetic mechanisms of core M3 glycan. The discovery of new glycan structures and the identification of highly regulated mechanisms of glycan processing will help researchers to understand glycan functions and develop therapeutic strategies for dystroglycanopathies.
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Academic Significance and Societal Importance of the Research Achievements |
コアM3糖鎖の欠損は先天性筋ジストロフィー症の原因となることから、本糖鎖の生合成機構および関連酵素の機能が明らかになったことで、難病である筋ジストロフィー症の病態解明および治療法開発への応用が期待される。また、新たな糖鎖構造や糖鎖合成制御機構の発見は、生体における糖鎖の役割の解明に寄与し、学術的にも重要な成果である。
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Report
(4 results)
Research Products
(65 results)
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[Journal Article] Cell endogenous activities of fukutin and FKRP coexist with the ribitol xylosyltransferase, TMEM5.2018
Author(s)
Nishihara, R., Kobayashi, K., Imae, R., Tsumoto, H., Manya, H., Mizuno, M., Kanagawa, M., Endo, T., and Toda, T.
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Journal Title
Biochemical and Biophysical Research Communications
Volume: 497
Issue: 4
Pages: 1025-1030
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] 3D structural analysis of protein O-mannosyl kinase, POMK, a causative gene product of dystroglycanopathy2017
Author(s)
M.Nagae, S.K.Mishra, M.Neyazaki, R.Oi, A.Ikeda, N.Matsugaki, S.Akashi, H.Manya, M.Mizuno, H.Yagi, K.Kato, T.Senda, T.Endo, T.Nogi, and Y.Yamaguchi
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Journal Title
Genes Cells
Volume: -
Issue: 4
Pages: 348-359
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] The muscular dystrophy gene TMEM5encodes a ribitol β1-4 Xylosyltransferase required for the functional glycosylation of dystroglycan.2016
Author(s)
Manya, H., Yamaguchi, Y., Kanagawa, M., Kobayashi, K., Tajiri, M., Akasaka-Manya, K., Kawakami, H., Mizuno, M., Wada, Y., Toda, T., and Endo, T.
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Journal Title
J. Biol. Chem
Volume: 291
Issue: 47
Pages: 24618-24627
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Carbohydrate-binding domain of the POMGnT1 stem region modulates O-mannosylation sites of α-dystroglycan.2016
Author(s)
Kuwabara N, Manya H, Yamada T, Tateno H, Kanagawa M, Kobayashi K, Akasaka-Manya K, Hirose Y, Mizuno M, Ikeguchi M, Toda T, Hirabayashi J, Senda T, Endo T, Kato R.
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Journal Title
Proc Natl Acad Sci U S A.
Volume: 113
Issue: 33
Pages: 9280-9285
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Analysis of phenotype, enzyme activity, and genotype of Chinese patients with POMT1 mutation2016
Author(s)
Haipo Yang, Hiroshi Manya, Kazuhiro Kobayashi, HUI JIAO, Xiaona Fu, Jiangxi Xiao, Xiaoqing Li, Jingmin wang, Yuwu Jiang, TATSUSHI TODA, Tamao Endo, Xiru Wu,Hui Xiong,
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Journal Title
J. Hum. Genet
Volume: 印刷中
Issue: 8
Pages: 753-759
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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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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[Presentation] Substrates recognition and oligomerization mechanism of Fukutin-related protein (FKRP).2018
Author(s)
N Kuwabara, H Manya, R Imae, T Tanaka, M Kanagawa, K Kobayashi, T Toda, M Mizuno, T Senda, T Endo, R Kato
Organizer
11th International Symposium on Glycosyltransferases
Related Report
Int'l Joint Research
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[Presentation] Carbohydrate-binding domain of the POMGnT1 stem region modulates O-mannosylation sites of α-dystroglycan2017
Author(s)
Naoyuki Kuwabara, Hiroshi Manya, Takeyuki Yamada, Hiroaki Tateno, Motoi Kanagawa, Kazuhiro Kobayashi, Keiko Akasaka-Manya, Yuriko Hirose, Mamoru Mizuno, Mitsunori Ikeguchi, Tatsushi Toda, Jun Hirabayashi, Toshiya Senda, Tamao Endo, Ryuichi Kato
Organizer
24th International Symposium on Glycoconjugates
Related Report
Int'l Joint Research
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[Presentation] 糖転移酵素POMGnT1の機能同定と糖鎖認識機構解析2016
Author(s)
桑原直之, 萬谷博, 山田健之, 舘野浩章, 金川基, 小林千浩, 萬谷-赤阪啓子, 弘瀬友理子, 水野真盛, 池口満徳, 戸田達史, 平林淳, 千田俊哉, 遠藤玉夫, 加藤龍一
Organizer
第39回日本分子生物学会年会
Place of Presentation
神奈川県横浜市(パシフィコ横浜)
Year and Date
2016-11-30
Related Report
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[Presentation] αジストログリカン糖鎖のリビトールリン酸タンデム構造とその生合成機構2016
Author(s)
小林千浩, 金川基, 田尻道子, 萬谷博, 久我敦, 山口芳樹, 萬谷-赤坂啓子, 古川潤一, 水野真盛, 川上宏子, 篠原康郎, 和田芳直, 遠藤玉夫, 戸田達史
Organizer
第39回日本分子生物学会年会
Place of Presentation
神奈川県横浜市(パシフィコ横浜)
Year and Date
2016-11-30
Related Report
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[Presentation] A novel carbohydrate binding domain of the POMGnT1 stem region modulates Omannosylation sites of α-dystroglycan2016
Author(s)
N Kuwabara, H Manya, T Yamada, H Tateno, Y Hirose, M Mizuno, M Ikeguchi, J Hirabayashi, T Senda, T Endo and R Kato
Organizer
10th International GLYCO T 2016 Conference
Place of Presentation
Toronto, Canada
Year and Date
2016-07-19
Related Report
Int'l Joint Research
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