Cytoplasmic γ-actin is not required for skeletal muscle development but its absence leads to a progressive myopathy
Cytoplasmic γ-actin is not required for skeletal muscle development but its absence leads to a progressive myopathy
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DOI：
10.1016/j.devcel.2006.07.001
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发表时间：
2006-09-01
影响因子：
11.8
通讯作者：
Ervasti, James M.
中科院分区：
文献类型：
--
作者：
Sonnemann, Kevin J.;Fitzsimons, Daniel P.;Ervasti, James M.
非肌肉伽玛（细胞）-肌动蛋白在骨骼肌中表达水平非常低，但独特地定位于肋节，即连接外周肌原纤维与肌膜的细胞骨架网络。我们生成并分析了骨骼肌特异性γ（细胞）-肌动蛋白敲除（Actg1-msKO）小鼠。尽管肌肉发育正常进行，但 Actg1-msKO 小鼠表现出明显的肌肉无力，并伴有进行性的肌纤维坏死/再生模式。观察到全身张力和等长抽搐力的功能缺陷，这与肌纤维和/或肌原纤维之间或肌腱连接处的连接缺陷一致。令人惊讶的是，缺乏γ（细胞）肌动蛋白的肌肉并未表现出几种肌营养不良症典型的纤维化、炎症和膜损伤，而是表现为一种新型的进行性肌病。总之，我们的数据证明了成人骨骼肌中含量最低但策略性定位的γ（细胞）-肌动蛋白的重要作用，并描述了一种新的小鼠模型来研究亚细胞肌动蛋白异构体分选的体内相关性。
Nonmuscle gamma(cyto)-actin is expressed at very low levels in skeletal muscle but uniquely localizes to costameres, the cytoskeletal networks that couple peripheral myofibrils to the sarcolemma. We generated and analyzed skeletal muscle-specific gamma(cyto)-actin knockout (Actg1-msKO) mice. Although muscle development proceeded normally, Actg1-msKO mice presented with overt muscle weakness accompanied by a progressive pattern of muscle fiber necrosis/regeneration. Functional deficits in whole-body tension and isometric twitch force were observed, consistent with defects in the connectivity between muscle fibers and/or myofibrils or at the myotendinous junctions. Surprisingly, gamma(cyto)-actin-deficient muscle did not demonstrate the fibrosis, inflammation, and membrane damage typical of several muscular dystrophies but rather presented with a novel progressive myopathy. Together, our data demonstrate an important role for minimally abundant but strategically localized gamma(cyto)-actin in adult skeletal muscle and describe a new mouse model to study the in vivo relevance of subcellular actin isoform sorting.