[Finding of O-mannosyl glycan in mammals and congenital muscular dystrophies due to glycosylation defects].
Most proteins within living organisms contain glycans. Glycan structures can modulate the biological properties and function of glycoproteins. Developments in glycobiology have revealed a new type of glycosidic linkage to the peptide portion, the O-mannosyl linkage in mammals, although heretofore it had been thought to be specific to yeast. One of the best known O-mannosyl-modified glycoproteins is dystroglycan, which is a central component of dystrophinglycoprotein complex isolated from skeletal muscle membranes. We identify and characterize a glycosyltransferase, UDP-N-acetylglucosamine: protein O-mannose beta 1,2-N-acetylglucosaminyltransferase (POMGnT1), involved in the biosynthesis of mammalian type O-mannosyl glycans. Finally, we find that the POMGnT1 gene is responsible for muscle-eye-brain disease (MEB). MEB is an autosomal recessive disorder characterized by congenital muscular dystrophy, ocular abnormalities and brain malformation (type II lissencephaly). Like MEB, recent data suggest that the aberrant protein glycosylation of a specific glycoprotein, alpha-dystroglycan, is the primary cause of some forms of congenital muscular dystrophy. Here I review the new insight into glycobiology of muscular dystrophy and neuronal migration disorder.
Endo
Tamao
T
Glycobiology Research Group, Tokyo Metropolitan Institute of Gerontology, Foundation for Research on Aging and Promotion of Human Welfare, 35-2 Sakae-cho, Itabashi-ku, Tokyo 173-0015, Japan. endo@tmig.or.jp
D000818:Animals; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000235:genetics; D049030:Dystroglycans; D006031:Glycosylation; D006801:Humans; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D009136:Muscular Dystrophies / Q000151:congenital* / Q000235:genetics*; D009154:Mutation; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics
D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; D008562:Membrane Glycoproteins; D049030:Dystroglycans; D017351:N-Acetylglucosaminyltransferases; C443106:protein O-mannose beta-1,2-N-acetylglucosaminyltransferase