Glycosylation defects: a new mechanism for muscular dystrophy?
| Autor: | Prabhjit K. Grewal, Jane E. Hewitt |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
musculoskeletal diseases
Genetics Glycosylation biology General Medicine medicine.disease Fukutin Muscular Dystrophies Cell biology chemistry.chemical_compound chemistry Laminin medicine biology.protein Dystroglycan Congenital muscular dystrophy Humans Muscular dystrophy Walker–Warburg syndrome Molecular Biology Genetics (clinical) Limb-girdle muscular dystrophy |
| Zdroj: | Human Molecular Genetics. 12:R259-R264 |
| ISSN: | 1460-2083 0964-6906 |
| Popis: | Recently, post-translational modification of proteins has been defined as a new area of focus for muscular dystrophy research by the identification of a group of disease genes that encode known or putative glycosylation enzymes. Walker-Warburg Syndrome (WWS) and muscle-eye-brain disease (MEB) are caused by mutations in two genes involved in O-mannosylation, POMT1 and POMGnT1, respectively. Fukuyama muscular dystrophy (FCMD) is due to mutations in fukutin, a putative phospholigand transferase. Congenital muscular dystrophy type 1C and limb girdle muscular dystrophy type 2I are allelic, both being due to mutations in the gene-encoding fukutin-related protein (FKRP). Finally, the causative gene in the myodystrophy (myd) mouse is a putative bifunctional glycosyltransferase (Large). WWS, MEB, FCMD and the myd mouse are also associated with neuronal migration abnormalities (often type II lissencephaly) and ocular or retinal defects. A deficiency in post-translational modification of alpha-dystroglycan is a common feature of all these muscular dystrophies and is thought to involve O-glycosylation pathways. This abnormally modified alpha-dystroglycan is deficient in binding to extracellular matrix ligands, including laminin and agrin. Selective deletion of dystroglycan in the central nervous system (CNS) produces brain abnormalities with striking similarities to WWS, MEB, FCMD and the myd mouse. Thus, impaired dystroglycan function is strongly implicated in these diseases. However, it is unlikely that these five glycosylation enzymes only have a role in glycosylation of alpha-dystroglycan and it is important that other protein targets are identified. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|