Functional analysis of orphan glycolsyltransferases associated with congenital muscular dystrophies using model organisms

2015 Fiscal Year Final Research Report

• Project/Area Number: 25670140
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: Nagoya University
• Principal Investigator: Okajima Tetsuya 名古屋大学, 医学(系)研究科(研究院), 教授 (20420383)
• Co-Investigator(Kenkyū-buntansha): KUROSAKA AKIRA 京都産業大学, 総合生命科学部, 教授 (90186536)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: α-Dystroglycan / GTDC2 / CTD110.6 / zebrafish

Outline of Final Research Achievements

Hypoglycosylation is a common characteristic of α-dystroglycanopathy, which is a group of congenital muscular dystrophies. More than ten genes, including GTDC2, have been implicated in α-dystroglycanopathies. In this study, we showed that GTDC2 generates CTD110.6 antibody-reactive N-acetylglucosamine (GlcNAc) epitopes on the α-dystroglycan (α-DG) within the mucin-like domain of α-DG in the endoplasmic reticulum. Mutations of GTDC2 identified in Walker-Warburg syndrome resulted in decreased glycosylation. Inactivation of GTDC2 function in zebrafish resulted in enlarged cerebral ventricle and microphthalmia, that is associated with dystroglycanopathy. Thus, GTDC2 is a novel glycosyltransferase catalyzing GlcNAcylation of α-DG in the endoplasmic reticulum. Zebrafish will serve as a suitable model organism to study GlcNAc modification of α-DG and to analyze defective O-glycosylation in α-dystroglycanopathies.

Free Research Field

生化学・糖鎖生物学