γ-Actin is required for cytoskeletal maintenance but not development
γ-Actin is required for cytoskeletal maintenance but not development
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DOI：
10.1073/pnas.0900221106
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发表时间：
2009-06-16
影响因子：
11.1
通讯作者：
Ervasti, James M.
中科院分区：
文献类型：
--
作者：
Belyantseva, Inna A.;Perrin, Benjamin J.;Ervasti, James M.
β（细胞）-肌动蛋白和γ（细胞）-肌动蛋白是普遍存在的蛋白质，被认为是所有非肌肉细胞中细胞骨架的基本构件。尽管这一广泛持有的假设，我们表明，γ（细胞）-肌动蛋白空小鼠（Actg 1（-/-））是可行的。然而，他们遭受增加的死亡率，并显示进行性听力损失在成年期，尽管补偿上调β（细胞）-肌动蛋白。年轻Actg 1（-/-）小鼠令人惊讶的生存能力和正常听力意味着β（细胞）-肌动蛋白可能会建立所有必要的非肌肉肌动蛋白为基础的细胞骨架结构，包括机械感觉毛细胞的静纤毛是必要的听力。虽然γ（细胞）肌动蛋白缺陷的静纤毛形式正常，我们发现，他们不能保持静纤毛肌动蛋白核心的完整性。在野生型中，γ（细胞）-肌动蛋白定位于沿着静纤毛的长度，但重新分布到由动物暴露于破坏性噪音引起的F-肌动蛋白核心破坏的位点。在Actg 1（-/-）静纤毛中，即使没有噪声暴露也观察到类似的破坏。我们的结论是，γ（细胞）-肌动蛋白是所需的F-肌动蛋白为基础的结构的加固和长期稳定性，但不是一个必不可少的积木的发展中的细胞骨架。
beta(cyto)-Actin and gamma(cyto)-actin are ubiquitous proteins thought to be essential building blocks of the cytoskeleton in all non-muscle cells. Despite this widely held supposition, we show that gamma(cyto)-actin null mice (Actg1(-/-)) are viable. However, they suffer increased mortality and show progressive hearing loss during adulthood despite compensatory up-regulation of beta(cyto)-actin. The surprising viability and normal hearing of young Actg1(-/-) mice means that beta(cyto)-actin can likely build all essential non-muscle actin-based cytoskeletal structures including mechanosensory stereocilia of hair cells that are necessary for hearing. Although gamma(cyto)-actin-deficient stereocilia form normally, we found that they cannot maintain the integrity of the stereocilia actin core. In the wild-type, gamma(cyto)-actin localizes along the length of stereocilia but re-distributes to sites of F-actin core disruptions resulting from animal exposure to damaging noise. In Actg1(-/-) stereocilia similar disruptions are observed even without noise exposure. We conclude that gamma(cyto)-actin is required for reinforcement and long-term stability of F-actin-based structures but is not an essential building block of the developing cytoskeleton.