title: Dystrobrevin deficiency at the sarcolemma of patients with muscular dystrophy.
abstract: Mutations in the genes encoding dystrophin or dystrophin-associated proteins are responsible for Duchenne muscular dystrophy or various forms of limb-girdle muscular dystrophies respectively. We have recently cloned the gene for the murine 87 kDa postsynaptic protein dystrobrevin, a dystrophin-associated protein. Anti-dystrobrevin antibodies stain the sarcolemma in normal skeletal muscle indicating that dystrobrevin co-localises with dystrophin and the dystrophin-associated protein complex. By contrast, dystrobrevin membrane staining is severely reduced in muscles of Duchenne muscular dystrophy patients, consistent with dystrobrevin being a dystrophin-associated protein. Interestingly, dystrobrevin staining at the sarcolemma is dramatically reduced in patients with limb-girdle muscular dystrophy arising from the loss of one or all of the sarcoglycan components. Normal dystrobrevin staining is observed in patients with other forms of limb-girdle muscular dystrophy where dystrophin and the rest of the dystrophin-associated protein complex are normally expressed and in other neuromuscular disorders. Our results show that dystrobrevin-deficiency is a generic feature of dystrophies linked to dystrophin and the dystrophin-associated proteins. This is the first indication that a cytoplasmic component of the dystrophin-associated protein complex may be involved in the pathogenesis of limb-girdle muscular dystrophy.
authors.affiliation: Department of Biochemistry, University of Oxford, UK.
authors.forename: L
authors.initials: L
authors.lastname: Metzinger
authors.forename: D J
authors.initials: DJ
authors.lastname: Blake
authors.forename: M V
authors.initials: MV
authors.lastname: Squier
authors.forename: L V
authors.initials: LV
authors.lastname: Anderson
authors.forename: A E
authors.initials: AE
authors.lastname: Deconinck
authors.forename: R
authors.initials: R
authors.lastname: Nawrotzki
authors.forename: D
authors.initials: D
authors.lastname: Hilton-Jones
authors.forename: K E
authors.initials: KE
authors.lastname: Davies
mesh_terms: D003598:Cytoskeletal Proteins / Q000378:metabolism; D049030:Dystroglycans; D016189:Dystrophin / Q000276:immunology / Q000378:metabolism; D049029:Dystrophin-Associated Proteins; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D009136:Muscular Dystrophies / Q000235:genetics*; D009479:Neuropeptides / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D049031:Sarcoglycans; D012508:Sarcolemma / Q000378:metabolism*
chemical_list: D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; C490915:DTNA protein, human; D016189:Dystrophin; D049029:Dystrophin-Associated Proteins; D008562:Membrane Glycoproteins; D009479:Neuropeptides; D049031:Sarcoglycans; C098885:dystrobrevin; D049030:Dystroglycans