Résumé :
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Plectin, a high molecular weight cytoskeletal linker protein (530 kDa), is widely distributed in mammalian tissues, with highest expression in squamous stratified epithelia, muscle and brain. Mutations of the human plectin (Plec1) gene on chromosome 8q24 cause epidermolysis bullosa simplex with muscular dystrophy (EBS-MD). This rare autosomal recessive disorder is characterized by blistering of skin and mucous membranes since birth and progressive muscular dystrophy manifesting from infancy to the fourth decade of life. Additional disease related features include brain atrophy, cataracts, urethral strictures, laryngeal webs, infantile respiratory complications and a myasthenic syndrome. The vast majority of Plec 1 mutations are clustered in exons 31 and 32, which encode the entire rod and C-terminal globular domains. As a consequence, the plectin protein expression in EBS-MD patients is either completely abolished or a mutant, non-functional plectin protein is expressed. This in turn leads to a structural and functional disorganization of the intermediate filament cytoskeleton. While the pathological changes in the skin of EBS-MD patients results from a faulty anchorage of cytokeratins to hemidesmosomes, the lack or expression of mutant plectin has a deleterious effect on the proper spacing, stabilisation and subcellular attachment of preformed desmin filaments in striated muscle. The severe structural changes in skin and muscle tissue in EBS-MD patients and plectin (-/-) mice indicate that plectin has an essential role in cells and tissues exposed to mechanical stress. Beyond an overview on the structural and functional role of plectin in normal and diseased striated skeletal muscle, this lecture will give insights into the relationship between the desmin and mitochondrial pathology in EBS-MD and myofibrillar myopathies.
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