GTDC2 modifies O-mannosylated ¦Á-dystroglycan in the endoplasmic reticulum to generate N-acetyl glucosamine epitopes reactive with CTD110.6 antibody
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- 作者：Mitsutaka Ogawa ; Naosuke Nakamura ; Yoshiaki Nakayama ; Akira Kurosaka ; Hiroshi Manya ; Motoi Kanagawa ; Tamao Endo ; Koichi Furukawa ; Tetsuya Okajima
- 关键词：¦Á-Dystroglycan ; GTDC2 ; CTD110.6 ; N-Acetylglucosamine
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：2013
- 出版时间：11 October, 2013
- 年：2013
- 卷：440
- 期：1
- 页码：88-93
- 全文大小：917 K
文摘
Hypoglycosylation is a common characteristic of dystroglycanopathy, which is a group of congenital muscular dystrophies. More than ten genes have been implicated in ¦Á-dystroglycanopathies that are associated with the defect in the O-mannosylation pathway. One such gene is GTDC2, which was recently reported to encode O-mannose ¦Â-1,4-N-acetylglucosaminyltransferase. Here we show that GTDC2 generates CTD110.6 antibody-reactive N-acetylglucosamine (GlcNAc) epitopes on the O-mannosylated ¦Á-dystroglycan (¦Á-DG). Using the antibody, we show that mutations of GTDC2 identified in Walker-Warburg syndrome and alanine-substitution of conserved residues between GTDC2 and EGF domain O-GlcNAc transferase resulted in decreased glycosylation. Moreover, GTDC2-modified GlcNAc epitopes are localized in the endoplasmic reticulum (ER). These data suggested that GTDC2 is a novel glycosyltransferase catalyzing GlcNAcylation of O-mannosylated ¦Á-DG in the ER. CTD110.6 antibody may be useful to detect a specific form of GlcNAcylated O-mannose and to analyze defective O-glycosylation in ¦Á-dystroglycanopathies.