Extensive but coordinated reorganization of the membrane skeleton in myofibers of dystrophic (mdx) mice.
Extensive but coordinated reorganization of the membrane skeleton in myofibers of dystrophic (mdx) mice.
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DOI：
10.1083/jcb.144.6.1259
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发表时间：
1999-03-22
影响因子：
7.8
通讯作者：
Bloch, R J
中科院分区：
文献类型：
--
作者：
Williams, M W;Bloch, R J
我们使用免疫荧光技术和共聚焦成像来研究mdx小鼠骨骼肌纤维的膜骨架的组织，mdx小鼠缺乏抗肌萎缩蛋白。β-Spectrin通常存在于肋肌的肌膜中，其是覆盖Z和M线的纵向链和元件的直线阵列。然而，在mdx小鼠的骨骼肌中，β-血影蛋白往往不存在于M线上的肌膜中，并且纵向链可能被破坏或缺失。膜和相关细胞骨架的其他蛋白质，包括syntrophin、β-肌营养不良蛋白聚糖、黏着斑蛋白和Na，K-ATP酶也集中在肋肌、对照肌纤维和mdx肌中。它们也分布在含有β-血影蛋白的相同改变的肌膜阵列中。在mdx肌肉中表达的Utrophin也与β-血影蛋白共同分布在突变的肌膜上。相比之下，结构和细胞内膜蛋白的分布，包括α-辅肌动蛋白，Ca-ATP酶和二氢吡啶受体，不受影响，即使在接近肌膜的部位。我们的研究结果表明，在mdx小鼠的肌纤维，膜相关的细胞骨架，但不是附近的肌浆，经历了广泛的协调变化的组织。这些变化可能导致营养不良肌肉肌膜的脆弱性。
We used immunofluorescence techniques and confocal imaging to study the organization of the membrane skeleton of skeletal muscle fibers of mdx mice, which lack dystrophin. β-Spectrin is normally found at the sarcolemma in costameres, a rectilinear array of longitudinal strands and elements overlying Z and M lines. However, in the skeletal muscle of mdx mice, β-spectrin tends to be absent from the sarcolemma over M lines and the longitudinal strands may be disrupted or missing. Other proteins of the membrane and associated cytoskeleton, including syntrophin, β-dystroglycan, vinculin, and Na,K-ATPase are also concentrated in costameres, in control myofibers, and mdx muscle. They also distribute into the same altered sarcolemmal arrays that contain β-spectrin. Utrophin, which is expressed in mdx muscle, also codistributes with β-spectrin at the mutant sarcolemma. By contrast, the distribution of structural and intracellular membrane proteins, including α-actinin, the Ca-ATPase and dihydropyridine receptors, is not affected, even at sites close to the sarcolemma. Our results suggest that in myofibers of the mdx mouse, the membrane- associated cytoskeleton, but not the nearby myoplasm, undergoes widespread coordinated changes in organization. These changes may contribute to the fragility of the sarcolemma of dystrophic muscle.