Molecular basis of regulation of nerve function by glycosylation

2015 Fiscal Year Final Research Report

• Project/Area Number: 25293016
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• 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)
• 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)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 糖鎖 / 筋ジストロフィー / O-マンノース / 糖転移酵素

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.

Free Research Field

糖鎖生物学