Disruption of dystroglycan axis by β-dystroglycan processing in cardiomyopathic hamster muscle

α-Dystroglycan is a cell surface peripheral membrane protein which binds to the extracellular matrix, while β-dystroglycan is a type I integral membrane protein which anchors α-dystroglycan to the cell membrane via the N-terminal extracellular domain. The complex composed of α- and β-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 β-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 β-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 β-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.