title: Syncoilin accumulation in two patients with desmin-related myopathy.
abstract: We have recently shown that syncoilin interacts with desmin in skeletal muscle and has a role in attaching and organising desmin filaments to the Z-lines. We have analysed patients with desmin accumulation and have found that syncoilin is both upregulated at the sarcolemma and aggregates with desmin indicating the presence of two distinct protein populations. Additional dystrophin-associated protein complex components also accumulate. The striking finding was that alpha-dystrobrevin-1 and neuronal nitric oxide synthase (nNOS) are almost completely lost from the membrane of these patients indicating that the myopathy may result from both the abnormal accumulation of proteins and an increase in ischaemic injury due to the loss of nNOS. We speculate that the loss of alpha-dystrobrevin from the membrane, and subsequent loss of nNOS, is due to the alpha-dystrobrevin-syncoilin-desmin interaction.
authors.affiliation: Department of Human Anatomy and Genetics, University of Oxford, South Parks Road, OX13QX, Oxford, UK.
authors.forename: Emily V
authors.initials: EV
authors.lastname: Howman
authors.forename: Nicky
authors.initials: N
authors.lastname: Sullivan
authors.forename: Ellen P
authors.initials: EP
authors.lastname: Poon
authors.forename: Joanna E
authors.initials: JE
authors.lastname: Britton
authors.forename: David
authors.initials: D
authors.lastname: Hilton-Jones
authors.forename: Kay E
authors.initials: KE
authors.lastname: Davies
mesh_terms: D000328:Adult; D001706:Biopsy; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003893:Desmin / Q000378:metabolism*; D016189:Dystrophin / Q000378:metabolism; D049029:Dystrophin-Associated Proteins; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007381:Intermediate Filament Proteins / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D009124:Muscle Proteins / Q000378:metabolism*; D009135:Muscular Diseases / Q000378:metabolism* / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D020033:Protein Isoforms; D012508:Sarcolemma / Q000378:metabolism / Q000473:pathology
chemical_list: D003598:Cytoskeletal Proteins; D003893:Desmin; D016189:Dystrophin; D049029:Dystrophin-Associated Proteins; D007381:Intermediate Filament Proteins; D008565:Membrane Proteins; D009124:Muscle Proteins; D020033:Protein Isoforms; C503784:SYNC protein, human; C098885:dystrobrevin; D019001:Nitric Oxide Synthase