Dystrobrevin deficiency at the sarcolemma of patients with muscular dystrophy.
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.
Metzinger
L
L
Department of Biochemistry, University of Oxford, UK.
Blake
D J
DJ
Squier
M V
MV
Anderson
L V
LV
Deconinck
A E
AE
Nawrotzki
R
R
Hilton-Jones
D
D
Davies
K E
KE
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*
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