Function of sugar chain in congenital muscular dystrophy

2015 Fiscal Year Final Research Report

• Project/Area Number: 26860682
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology
• Principal Investigator: Yamada Takeyuki 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 (40725199)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: O-マンノース型糖鎖

Outline of Final Research Achievements

O-mannose-type glycosylation of a-dystroglycan (a-DG) is required for its extracellular matrix binding activities. Aberrant a-DG glycosylation causes congenital muscular dystrophy (CMD), accompanying neurological and ocular abnormalities. Here, we identified novel mutations in POMGNT1, which encodes an essential component in O-mannosylation pathway, in retinitis pigmentosa. Enzymatic assay showed that the mutants POMGNT1 impaired its enzymatic activities, with only 10 to 30% of the wild type level retained. On the other hand, mutants POMGNT1 identified from CMD nearly abolished its enzymatic activities. These results suggest that a few O-mannose-type glycosylation syntheses suppress CMD, but develop RP.

Free Research Field

分子生物学