Deficiency of alpha-dystroglycan in muscle-eye-brain disease.

Abstract

Alpha-dystroglycan is a component of the dystrophin-glycoprotein-complex, which is the major mechanism of attachment between the cytoskeleton and the extracellular matrix. Muscle-eye-brain disease (MEB) is an autosomal recessive disorder characterized by congenital muscular dystrophy, ocular abnormalities and lissencephaly. We recently found that MEB is caused by mutations in the protein O-linked mannose beta1,2-N-acetylglucosaminyltransferase (POMGnT1) gene. POMGnT1 is a glycosylation enzyme that participates in the synthesis of O-mannosyl glycan, a modification that is rare in mammals but is known to be a laminin-binding ligand of alpha-dystroglycan. Here we report a selective deficiency of alpha-dystroglycan in MEB patients. This finding suggests that alpha-dystroglycan is a potential target of POMGnT1 and that altered glycosylation of alpha-dystroglycan may play a critical role in the pathomechanism of MEB and some forms of muscular dystrophy.

• Authors: Hiroki Kano, Kazuhiro Kobayashi, Ralf Herrmann, Masaji Tachikawa, Hiroshi Manya, Ichizo Nishino, Ikuya Nonaka, Volker Straub, Beril Talim, Thomas Voit, Haluk Topaloglu, Tamao Endo, Hideki Yoshikawa, Tatsushi Toda
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 291 Issue 5 Pg. 1283-6 (Mar 15 2002) ISSN: 0006-291X [Print] United States
• PMID: 11883957 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (C)2002 Elsevier Science (USA).

Chemical References

• Cytoskeletal Proteins
• DAG1 protein, human
• Membrane Glycoproteins
• Dystroglycans
• N-Acetylglucosaminyltransferases
• protein O-mannose beta-1,2-N-acetylglucosaminyltransferase

Topics

• Child
• Child, Preschool
• Cytoskeletal Proteins (deficiency, metabolism)
• Dystroglycans
• Humans
• Immunohistochemistry
• Infant
• Membrane Glycoproteins (deficiency, metabolism)
• Muscle, Skeletal (metabolism)
• Muscular Dystrophies (metabolism)
• Myopia (metabolism)
• N-Acetylglucosaminyltransferases (metabolism)