title: Role of gelatinases in pathological and physiological processes involving the dystrophin-glycoprotein complex.
abstract: Dystrophin is a cytosolic protein belonging to a membrane-spanning glycoprotein complex, called dystrophin-glycoprotein complex (DGC) that is expressed in many tissues, especially in skeletal muscle and in the nervous system. The DGC connects the cytoskeleton to the extracellular matrix and, although none of the proteins of the DGC displays kinase or phosphatase activity, it is involved in many signal transduction pathways. Mutations in some components of the DGC are linked to many forms of inherited muscular dystrophies. In particular, a mutation in the dystrophin gene, leading to a complete loss of the protein, provokes one of the most prominent muscular dystrophies, the Duchenne muscular dystrophy, which affects 1 out of 3500 newborn males. What is observed in these circumstances, is a dramatic alteration of the expression levels of a multitude of metalloproteinases (MMPs), a family of extracellular Zn(2+)-dependent endopeptidases, in particular of MMP-2 and MMP-9, also called gelatinases. Indeed, the enzymatic activity of MMP-2 and MMP-9 on dystroglycan, an important member of the DGC, plays a significant role also in physiological processes taking place in the central and peripheral nervous system. This mini-review discusses the role of MMP-2 and MMP-9, in physiological as well as pathological processes involving members of the DGC.
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
authors.affiliation: Istituto di Chimica del Riconoscimento Molecolare (CNR) c/o Istituto di Biochimica e Biochimica Clinica, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Sciandra
authors.affiliation: Istituto di Chimica del Riconoscimento Molecolare (CNR) c/o Istituto di Biochimica e Biochimica Clinica, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Brancaccio
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000201:enzymology; D049030:Dystroglycans / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009136:Muscular Dystrophies / Q000201:enzymology; D017933:Peripheral Nervous System / Q000201:enzymology
chemical_list: D049030:Dystroglycans; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Duchenne muscular dystrophy; Dystroglycan; Dystrophin; Dystrophin–glycoprotein complex; Gelatinase; Metalloproteinase