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Length regulation of mechanosensitive stereocilia depends on very slow actin dynamics and filament-severing proteins

机译:机械敏感的立体纤毛的长度调节取决于极慢的肌动蛋白动力学和细丝切断蛋白

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摘要

Auditory sensory hair cells depend on stereocilia with precisely regulated lengths to detect sound. Since stereocilia are primarily composed of crosslinked, parallel actin filaments, regulated actin dynamics are essential for controlling stereocilia length. Here we assessed stereocilia actin turnover by monitoring incorporation of inducibly expressed β-actin-GFP in adult mouse hair cells in vivo and by directly measuring β-actin-GFP turnover in explants. Stereocilia actin incorporation is remarkably slow and restricted to filament barbed ends in a small tip compartment, with minimal accumulation in the rest of the actin core. Shorter rows of stereocilia, which have mechanically gated ion channels, show more variable actin turnover than the tallest stereocilia, which lack channels. Finally, the proteins ADF and AIP1, which both mediate actin filament severing, contribute to stereocilia length maintenance. Altogether, the data support a model whereby stereocilia actin cores are largely static, with dynamic regulation at the tips to maintain a critical length.
机译:听觉感觉毛细胞依靠具有精确调节长度的立体毛发来检测声音。由于纤毛主要由交联的平行肌动蛋白丝组成,因此调节肌动蛋白动力学对于控制纤毛的长度至关重要。在这里,我们通过监测体内成年小鼠毛细胞中诱导表达的β-肌动蛋白-GFP的掺入以及通过直接测量外植体中β-肌动蛋白-GFP的代谢,来评估立体纤毛肌动蛋白的代谢。立体定向肌动蛋白的掺入非常缓慢,并且限制在小尖端隔室中的带刺丝末端,在肌动蛋白核心的其余部分中的积累最少。与没有通道的最高立体睫毛相比,具有机械门控离子通道的较短的立体睫毛行显示出更多的肌动蛋白周转率。最后,介导肌动蛋白丝切断的蛋白质ADF和AIP1有助于维持纤毛长度。总体而言,数据支持一个模型,其中,纤毛肌动蛋白核心在很大程度上是静态的,尖端具有动态调节作用,以维持临界长度。

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