Induction of dystrophin-associated proteins together with nicotinic acetylcholine receptors by denervation in the absence of dystrophin in skeletal muscles of mdx mice.
We purified the nicotinic acetylcholine receptor from digitonin-solubilized rabbit skeletal muscle by affinity chromatography and detected many proteins linked to AChR, including dystrophin, adhalin, beta-dystroglycan, utrophin, rapsyn, and actin. To determine whether or not AChR links to dystrophin-associated proteins (DAPs) without dystrophin, we studied the effects of denervation on AChR and DAPs in the skeletal muscle of a mdx mouse. Following surgical denervation, the levels of adhalin and beta-dystroglycan dramatically increased at the extrajunctional sarcolemma with AChR, suggesting that their association is independent of dystrophin. Furthermore, the diffuse extrajunctional appearance of adhalin, beta-dystroglycan, and AChR was observed after pharmacological denervation through the subcutaneous administration of succinylcholine. Since the depletion of DAPs and the subsequent disruption of sarcolemmal linkage are believed to be a primary cause of muscle cell necrosis in dystrophinopathies, pharmacological denervation may have some beneficial effect on these diseases.
Mitsui
T
T
First Department of Internal Medicine, School of Medicine, University of Tokushima, Japan.
Kawai
H
H
Kawajiri
M
M
Kunishige
M
M
Aki
K
K
Saito
S
S
D000595:Amino Acid Sequence; D000818:Animals; D002846:Chromatography, Affinity; D002848:Chromatography, DEAE-Cellulose; D003714:Denervation; D016189:Dystrophin / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000096:biosynthesis*; D018482:Muscle, Skeletal / Q000294:innervation / Q000378:metabolism*; D009137:Muscular Dystrophy, Animal / Q000378:metabolism; D011817:Rabbits; D011978:Receptors, Nicotinic / Q000096:biosynthesis* / Q000302:isolation & purification
D016189:Dystrophin; D009124:Muscle Proteins; D011978:Receptors, Nicotinic