Alpha-dystroglycan is a potential target of matrix metalloproteinase MMP-2

Dystroglycan (DG) is a member of the glycoprotein complex associated to dystrophin and composed by two subunits, the ?-DG, a transmembrane protein, and the ?-DG, an extensively glycosylated extracellular protein. The ?-DG ectodomain degradation by the matrix metallo-proteinases (i.e., MMP-2 and MMP-9) in both, pathological and physiological conditions, has been characterized in detail in previous publications. Since the amounts of ?-DG and ?-DG at the cell surface decrease when gelatinases are up-regulated, we investigated the degradation of ?-DG subunit by MMP-2. Present data show, for the first time, that the proteolysis of ?-DG indeed occurs on a native glycosylated molecule enriched from rabbit skeletal muscle. In order to characterize the ?-DG portion, which is more prone to cleavage by MMP-2, we performed different degradations on tailored recombinant domains of ?-DG spanning the whole subunit. The overall bulk of results casts light on a relevant susceptibility of the ?-DG to MMP-2 degradation with particular reference to its C-terminal domain, thus opening a new scenario on the role of gelatinases (in particular of MMP-2) in the degradation of this glycoprotein complex, taking place in the course of pathological processes.