AGO61-dependent GlcNAc Modification Primes the Formation of Functional Glycans on α-dystroglycan

Overview

Journal Sci Rep

Specialty Science

Date 2013 Nov 22

PMID 24256719

Citations 20

Authors

Hirokazu Yagi

Naoki Nakagawa

Takuya Saito

Hiroshi Kiyonari

Takaya Abe

Tatsushi Toda

Sz-Wei Wu

Kay-Hooi Khoo

Shogo Oka

Koichi Kato

Affiliations

Soon will be listed here.

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.

Citing Articles

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