Matsumura K, Burghes A H, Mora M, Tomé F M, Morandi L, Cornello F, Leturcq F, Jeanpierre M, Kaplan J C, Reinert P
Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City 52242.
J Clin Invest. 1994 Jan;93(1):99-105. doi: 10.1172/JCI116989.
The absence of dystrophin causes the drastic reduction of the dystrophin-associated proteins (DAPs) in the sarcolemma and the loss of the linkage between the subsarcolemmal cytoskeleton and the extracellular matrix in Duchenne muscular dystrophy (DMD) skeletal muscle. Here, we report a mild reduction of the DAPs in the unique Becker muscular dystrophy patients with huge deletions in the rod domain of dystrophin and a moderate reduction of the DAPs in patients with huge deletions that involve both the NH2-terminal and rod domains of dystrophin. The phenotype of the latter patients was more severe than that of the former. In both cases, however, the reduction in the DAPs was milder than in typical DMD patients or DMD patients lacking the COOH-terminal domains of dystrophin. Our results suggest that (a) the NH2-terminal and rod domains of dystrophin may not be essential for the interaction with the sarcolemmal glycoprotein complex; and (b) defects in the actin binding activity of dystrophin may cause disruption of the anchorage of the dystrophin-glycoprotein complex to the subsarcolemmal cytoskeleton, which may render muscle fibers susceptible to degeneration.
在杜兴氏肌营养不良症（DMD）骨骼肌中，抗肌萎缩蛋白的缺失导致肌膜中抗肌萎缩蛋白相关蛋白（DAPs）急剧减少，以及肌膜下细胞骨架与细胞外基质之间的连接丧失。在此，我们报告了在抗肌萎缩蛋白杆状结构域存在巨大缺失的独特贝克氏肌营养不良症患者中，DAPs有轻度减少，以及在抗肌萎缩蛋白的NH2末端和杆状结构域均有巨大缺失的患者中，DAPs有中度减少。后一组患者的表型比前一组更严重。然而，在这两种情况下，DAPs的减少都比典型DMD患者或缺乏抗肌萎缩蛋白COOH末端结构域的DMD患者更轻。我们的结果表明：（a）抗肌萎缩蛋白的NH2末端和杆状结构域对于与肌膜糖蛋白复合物的相互作用可能不是必需的；（b）抗肌萎缩蛋白的肌动蛋白结合活性缺陷可能导致抗肌萎缩蛋白 - 糖蛋白复合物与肌膜下细胞骨架的锚定破坏，这可能使肌纤维易于发生变性。
