Matrix Metalloproteinase Activity that Disrupts the Dystroglycan Complex: Its Role in the Molecular Pathogenesis of Muscular Dystrophies

The dystroglycan (DG) complex, composed of two subunits αDG and βDG, interacts with the sarcoglycan complex to form the dystrophin-glycoprotein complex. αDG is a cell surface peripheral membrane protein which binds to the components of the extracellular matrix, while βDG is a type I integral membrane protein which anchors αDG to the cell membrane via the N-terminal extracellular domain. Although defects of the DG gene have not been identified as the primary causes of hereditary diseases in humans, secondary but significant abnormalities of the DG complex have been revealed in a number of muscular dystrophies. In this article, we characterize the matrix metalloproteinase (MMP) activity that disrupts the DG complex by cleaving the extracellular domain of βDG and discuss if this MMP plays a role in the molecular pathogenesis of muscular dystrophies. We also address the therapeutic potential of the drugs that inhibit this MMP activity to decelerate muscle degeneration in these diseases.