title: Cytoskeletal derangements in hereditary myopathy with a desmin L345P mutation.
abstract: Patients with abnormal accumulations of desmin have been described in myopathies with or without cardiac involvement. Desmin deposits were sometimes associated with abnormal aggregates of other cytoskeletal proteins. In the present study we present how the cytoskeletal organisation of desmin, nestin, synemin, paranemin, plectin and alphaB-crystallin is altered in skeletal muscles from a patient with a L345P mutation in the desmin gene. In general, accumulations of desmin together with synemin, nestin, plectin and alphaB-crystallin were present between myofibrils and beneath the sarcolemma. However, as the biopsy samples were very myopathic, large variability in fibre size and fibre maturation was seen, thus the myofibrillar content and the cytoskeletal organisation varied considerably. In cultured satellite cells from the patient, desmin aggregates were not observed in initial passages, but occurred over time in culture in the form of perinuclear, peripheral or cytoplasmic deposits. Nestin colocalised to the abnormal desmin deposits to a larger extent than did vimentin. alphaB-Crystallin was only present in cells with a disrupted desmin network. Plectin was altered in a subset of cells with a disrupted desmin network, whereas synemin and paranemin were not detected. We conclude that the L345P desmin mutation has a profound influence on the cytoskeletal organisation both in vivo and in vitro, which reflects the pathogenesis of the desmin myopathy.
authors.affiliation: Centre for Musculoskeletal Research, National Institute for Working Life, 907 13 Umeå, Sweden.
authors.forename: Lena
authors.initials: L
authors.lastname: Carlsson
authors.forename: Christine
authors.initials: C
authors.lastname: Fischer
authors.forename: Gunnnar
authors.initials: G
authors.lastname: Sjöberg
authors.forename: Richard M
authors.initials: RM
authors.lastname: Robson
authors.forename: Thomas
authors.initials: T
authors.lastname: Sejersen
authors.forename: Lars-Eric
authors.initials: LE
authors.lastname: Thornell
mesh_terms: D002478:Cells, Cultured; D003893:Desmin / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000378:metabolism; D007382:Intermediate Filaments / Q000378:metabolism* / Q000473:pathology; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009135:Muscular Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D009154:Mutation; D009419:Nerve Tissue Proteins; D064231:Nestin; D051190:Plectin; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism / Q000473:pathology; D038203:alpha-Crystallin B Chain / Q000378:metabolism
chemical_list: D003893:Desmin; D007381:Intermediate Filament Proteins; D009124:Muscle Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; D064231:Nestin; C495332:PLEC protein, human; D051190:Plectin; D038203:alpha-Crystallin B Chain; C430456:desmuslin