Deficiency of alpha-dystroglycan in muscle-eye-brain disease |
| |
Authors: | Kano Hiroki Kobayashi Kazuhiro Herrmann Ralf Tachikawa Masaji Manya Hiroshi Nishino Ichizo Nonaka Ikuya Straub Volker Talim Beril Voit Thomas Topaloglu Haluk Endo Tamao Yoshikawa Hideki Toda Tatsushi |
| |
Institution: | Division of Functional Genomics, Osaka University Graduate School of Medicine, 2-2 B9, Yamadaoka, Suita, Osaka 565-0871, Japan. |
| |
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. |
| |
Keywords: | muscle-eye-brain disease muscular dystrophy dystroglycan glycosylation POMGnT1 neuronal migration disorder |
本文献已被 ScienceDirect PubMed 等数据库收录! |