Molecular Basis Of Transduction In Auditory Sensory Orga

听觉和平衡依赖于感觉毛细胞，这些感觉毛细胞配备有机械敏感的微绒毛样细胞器，称为静纤毛，能够通过位于其尖端的机械门控通道检测纳米尺度的位移。哺乳动物的听毛细胞是终末分化的，不能再生。虽然它们的静纤毛对机械振动非常敏感，结构有序，容易受到过度刺激的破坏，但它们一生都保持着正常的工作状态。每个静纤毛由数百个平行的、均匀极化的、规则交联的肌动蛋白丝组成的刚性准晶体阵列支撑。肌动蛋白丝的方向是，正端（带倒钩）位于静纤毛的顶端，负端（带尖）位于基部。肌动蛋白的这种组织与微绒毛和丝状伪足中的肌动蛋白形成有许多共同的构建原理，但可以高达120？m的长度。这种有序的肌动蛋白形成是如何建立、调节和更新的，在很大程度上是未知的。我们现在已经证明，位于毛细胞感觉静纤毛核心的看似静止的肌动蛋白类晶体，通过在静纤毛尖端自我复制、向后旋转和在基部自我分解而不断更新。跑步是肌动蛋白丝的动态行为，在各种形式的细胞运动中起着至关重要的作用。然而，很少有人知道这个过程中的发生和调节非运动肌动蛋白组件。我们表明，跑步机率缩放到静纤毛的长度和调制的本地物理参数，如张力的封装膜和静纤毛链接，以及位于尖端和旁边的肌动蛋白paracrytic肌球蛋白。我们认为，这种调节性的神经铣削动态地塑造了静纤毛的功能结构，并在过度刺激的恢复中起着核心作用。这样一个动态的观点，一个paracrystalline肌动蛋白合奏强调如何组织良好的细胞结构可以保持稳定状态的结构，自我调整，并修复，同时进行持续的自我更新。

Hearing and balance depend on sensory hair cells equipped with mechanosensitive, microvilli-like organelles, called stereocilia, that are capable of detecting displacements on a nanometer scale through mechanically gated channels located at their tips. Mammalian auditory hair cells are terminally differentiated and do not regenerate. While their stereocilia are exquisitely sensitive to mechanical vibration, orderly structured, and easily damaged by over-stimulation, they are maintained in proper working order for a lifetime. Each stereocilium is supported by a rigid paracrystalline array of several hundred parallel, uniformly polarized and regularly cross-linked actin filaments. The actin filaments are oriented such that the plus (barbed) ends are at the tips of the stereocilia and the minus (pointed) ends at the base. This organization of actin shares many construction principles with the actin formations in microvilli and filopodia yet can be up to 120?m in length. How such ordered actin formations are built, regulated, and renewed is largely unknown. We have now demonstrated that the seemingly static actin paracrystal at the core of sensory stereocilia of hair cells, undergoes continuous renewal enabled by reproducing itself at the stereocilia tips, treadmilling rearwards, and dismantling itself at the base. Treadmilling is a dynamic behavior of actin filaments that plays a crucial role in various forms of cell motility. However, little is known about the occurrence and regulation of this process in non-motile actin assemblies. We show that treadmill rates are scaled to the length of stereocilia and are modulated by local physical parameters, such as tension on the encapsulating membrane and on stereocilia links, as well as by myosins located at the tips and alongside the actin paracrystal. We propose that this regulated treadmilling dynamically shapes the functional architecture of stereocilia and plays a central role in recovery from over-stimulation. Such a dynamic view of a paracrystalline actin ensemble highlights how well organized cellular structures can maintain steady state structure, self-adjustment, and repair while undergoing continuous self-renewal.