Aberrant glycosylation of alpha-dystroglycan and congenital muscular dystrophies.
Dystroglycan is encoded by a single gene and is cleaved into two proteins, alpha- and beta-dystroglycan, by posttranslational processing. In skeletal muscle, dystroglycan is a component of the dystrophin-glycoprotein complex. alpha-Dystroglycan is an extracellular peripheral membrane glycoprotein that binds to beta-dystroglycan, which is a transmembrane glycoprotein. alpha-Dystroglycan is heavily glycosylated and its sugars have a role in binding to laminin, neurexin and agrin. The main glycan of alpha-dystroglycan was found to be O-mannosylglycan which is a ligand of laminin. We identified and characterized two glycosyltransferases involved in the biosynthesis of O-mannosylglycans. These two enzymes are responsible for congenital muscular dystrophies, muscle-eye-brain disease and Walker-Warburg syndrome. These results indicate that O-mannosylation of alpha-dystroglycan is important in muscle and brain development. This review describes the relation between aberrant glycosylation of alpha-dystroglycan and congenital muscular dystrophies.
Endo
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Glycobiology Research Group, Tokyo Metropolitan Institute of Gerontology, Foundation for Research on Aging and Promotion of Human Welfare. endo@tmig.or.jp
D049030:Dystroglycans / Q000235:genetics* / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D008364:Mannosyltransferases / Q000235:genetics; D009136:Muscular Dystrophies / Q000235:genetics* / Q000378:metabolism; D020294:Myasthenic Syndromes, Congenital / Q000235:genetics* / Q000378:metabolism
C483081:DAG1 protein, human; D049030:Dystroglycans; D008364:Mannosyltransferases; C082696:protein O-mannosyltransferase