AGO61-dependent GlcNAc modification primes the formation of functional glycans on α-dystroglycan.

• Yagi, Hirokazu

• Nakagawa, Naoki

• Saito, Takuya

• Kiyonari, Hiroshi

• Abe, Takaya

• Toda, Tatsushi

• Wu, Sz-Wei

• Khoo, Kay-Hooi

• Oka, Shogo

• Kato, Koichi

Abstract

Dystroglycanopathy is a major class of congenital muscular dystrophy that is caused by a deficiency of functional glycans on α-dystroglycan (α-DG) with laminin-binding activity. A product of a recently identified causative gene for dystroglycanopathy, AGO61, acted in vitro as a protein O-mannose β-1, 4-N-acetylglucosaminyltransferase, although it was not functionally characterized. Here we show the phenotypes of AGO61-knockout mice and demonstrate that AGO61 is indispensable for the formation of laminin-binding glycans of α-DG. AGO61-knockout mouse brain exhibited abnormal basal lamina formation and a neuronal migration defect due to a lack of laminin-binding glycans. Furthermore, our results indicate that functional α-DG glycosylation was primed by AGO61-dependent GlcNAc modifications of specific threonine-linked mannosyl moieties of α-DG. These findings provide a key missing link for understanding how the physiologically critical glycan motif is displayed on α-DG and provides new insights on the pathological mechanisms of dystroglycanopathy.

Journal

• Scientific reports

  Scientific reports 3 2013-11-21

  Nature Publishing Group

Keywords

• Glycobiology
• Transferases

Details

• CRID: 1050282810757246720
• NII Article ID: 120005353504
• ISSN: 20452322
• HANDLE: 2433/179778
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • CiNii Articles