title: Disruption of dystroglycan axis by beta-dystroglycan processing in cardiomyopathic hamster muscle.
abstract: Alpha-dystroglycan is a cell surface peripheral membrane protein which binds to the extracellular matrix, while beta-dystroglycan is a type I integral membrane protein which anchors alpha-dystroglycan to the cell membrane via the N-terminal extracellular domain. The complex composed of alpha- and beta-dystroglycan is called the dystroglycan complex. Although defects of the dystroglycan gene have not been identified as the primary causes of hereditary diseases in humans, secondary but significant abnormalities of the dystroglycan complex have been revealed in severe muscular dystrophies, including sarcoglycanopathy (LGMD2C, D, E and F). In this study, we investigated proteolytic processing of beta-dystroglycan and its effect on the extracellular matrix-cell membrane linkage in cardiomyopathic hamsters, the model animals of LGMD2F. Compared to normal controls, proteolytic processing of beta-dystroglycan was activated in the skeletal, cardiac and smooth muscles of cardiomyopathic hamsters and this resulted in the partial disruption of the dystroglycan complex in these tissues. These phenomena were observed from the early phase of muscle degeneration process. Our results suggest that proteolytic processing of beta-dystroglycan disrupts the extracellular matrix-cell membrane linkage via the dystroglycan complex and this may play a role in the molecular pathogenesis of muscle degeneration in cardiomyopathic hamsters.
authors.affiliation: Department of Neurology and Neuroscience, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan. k-matsu@med.teikyo-u.ac.jp
authors.forename: Kiichiro
authors.initials: K
authors.lastname: Matsumura
authors.forename: Ken
authors.initials: K
authors.lastname: Arai
authors.forename: Di
authors.initials: D
authors.lastname: Zhong
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Saito
authors.forename: Hiroko
authors.initials: H
authors.lastname: Fukuta-Ohi
authors.forename: Ryuji
authors.initials: R
authors.lastname: Maekawa
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yamada
authors.forename: Teruo
authors.initials: T
authors.lastname: Shimizu
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D009202:Cardiomyopathies / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D006224:Cricetinae; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D019281:Dimerization; D004195:Disease Models, Animal; D049030:Dystroglycans; D005109:Extracellular Matrix / Q000378:metabolism; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009130:Muscle, Smooth / Q000378:metabolism / Q000473:pathology; D009132:Muscles / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010447:Peptide Hydrolases / Q000378:metabolism; D051381:Rats
chemical_list: D003598:Cytoskeletal Proteins; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D049030:Dystroglycans; D010447:Peptide Hydrolases