Association of dystrophin-related protein with dystrophin-associated proteins in mdx mouse muscle.
Dystrophin is associated with a complex of muscle membrane (sarcolemmal) glycoproteins that provide a linkage to the extracellular matrix protein, laminin. The absence of dystrophin leads to a dramatic reduction of the dystrophin-associated proteins (156DAG, 59DAP, 50DAG, 43DAG and 35DAG) in the sarcolemma of patients with Duchenne muscular dystrophy and mdx mice. Here we demonstrate that dystrophin-related protein (DRP, utrophin), an autosomal homologue of dystrophin, is associated with an identical or antigenically similar complex of sarcolemmal proteins and that DRP and the dystrophin/DRP-associated proteins colocalize to the neuromuscular junction in Duchenne muscular dystrophy and mdx muscle. The DRP and dystrophin/DRP-associated proteins are found throughout the sarcolemma in small-calibre skeletal muscles and cardiac muscle of adult mdx mice. Because these muscles show minimal pathological changes, our results could provide a basis for the upregulation of DRP as a potential therapeutic approach.
Matsumura
K
K
Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City 52242.
Ervasti
J M
JM
Ohlendieck
K
K
Kahl
S D
SD
Campbell
K P
KP
D000818:Animals; D002499:Centrifugation, Density Gradient; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000378:metabolism*; D016189:Dystrophin / Q000032:analysis / Q000378:metabolism*; D006023:Glycoproteins / Q000032:analysis / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008565:Membrane Proteins; D051379:Mice; D009124:Muscle Proteins / Q000032:analysis / Q000378:metabolism*; D009132:Muscles / Q000737:chemistry / Q000648:ultrastructure; D009136:Muscular Dystrophies / Q000378:metabolism; D009137:Muscular Dystrophy, Animal / Q000378:metabolism*; D009206:Myocardium / Q000737:chemistry; D009469:Neuromuscular Junction / Q000737:chemistry / Q000378:metabolism; D012508:Sarcolemma / Q000737:chemistry / Q000378:metabolism; D014018:Tissue Distribution; D049411:Utrophin
D003598:Cytoskeletal Proteins; D016189:Dystrophin; D006023:Glycoproteins; D008565:Membrane Proteins; D009124:Muscle Proteins; C483600:Utrn protein, mouse; D049411:Utrophin