title: α-dystroglycan is a potential target of matrix metalloproteinase MMP-2.
abstract: Dystroglycan (DG) is a member of the glycoprotein complex associated to dystrophin and composed by two subunits, the β-DG, a transmembrane protein, and the α-DG, an extensively glycosylated extracellular protein. The β-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 α-DG and β-DG at the cell surface decrease when gelatinases are up-regulated, we investigated the degradation of α-DG subunit by MMP-2. Present data show, for the first time, that the proteolysis of α-DG indeed occurs on a native glycosylated molecule enriched from rabbit skeletal muscle. In order to characterize the α-DG portion, which is more prone to cleavage by MMP-2, we performed different degradations on tailored recombinant domains of α-DG spanning the whole subunit. The overall bulk of results casts light on a relevant susceptibility of the α-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.
authors.affiliation: Dipartimento di Scienze Cliniche e Medicina Traslazionale, Universita` di Roma Tor Vergata, Rome, Italy; Centro di Biomedicina Spaziale, Università di Roma Tor Vergata, Rome, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Sbardella
authors.affiliation: Istituto di Chimica del Riconoscimento Molecolare (CNR) c/c Istituto di Biochimica e Biochimica Clinica, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Sciandra
authors.affiliation: Dipartimento di Scienze Cliniche e Medicina Traslazionale, Universita` di Roma Tor Vergata, Rome, Italy; Centro di Biomedicina Spaziale, Università di Roma Tor Vergata, Rome, Italy.
authors.forename: Magda
authors.initials: M
authors.lastname: Gioia
authors.affiliation: Dipartimento di Scienze Cliniche e Medicina Traslazionale, Universita` di Roma Tor Vergata, Rome, Italy; Centro di Biomedicina Spaziale, Università di Roma Tor Vergata, Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Marini
authors.affiliation: Istituto di Chimica del Riconoscimento Molecolare (CNR), Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Gori
authors.affiliation: Istituto di Biochimica e Biochimica Clinica, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Giardina
authors.affiliation: Dipartimento di Scienze Cliniche e Medicina Traslazionale, Universita` di Roma Tor Vergata, Rome, Italy; Centro di Biomedicina Spaziale, Università di Roma Tor Vergata, Rome, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Tarantino
authors.affiliation: Dipartimento di Scienze Cliniche e Medicina Traslazionale, Universita` di Roma Tor Vergata, Rome, Italy; Centro di Biomedicina Spaziale, Università di Roma Tor Vergata, Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Coletta
authors.affiliation: Istituto di Chimica del Riconoscimento Molecolare (CNR) c/c Istituto di Biochimica e Biochimica Clinica, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Brancaccio
authors.affiliation: Istituto di Biochimica e Biochimica Clinica, Università Cattolica del Sacro Cuore, Rome, Italy. Electronic address: manuela.bozzi@rm.unicatt.it.
authors.forename: Manuela
authors.initials: M
authors.lastname: Bozzi
mesh_terms: D000818:Animals; D049030:Dystroglycans / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018093:Gelatinases / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D008958:Models, Molecular; D018482:Muscle, Skeletal / Q000378:metabolism*; D059748:Proteolysis; D011817:Rabbits; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D011994:Recombinant Proteins; D049030:Dystroglycans; D018093:Gelatinases; D020778:Matrix Metalloproteinase 2
keywords: Dystroglycan; MMP-2; Metalloproteinase