The actin-binding proteins eps8 and gelsolin have complementary roles in regulating the growth and stability of mechanosensory hair bundles of mammalian cochlear outer hair cells.
The actin-binding proteins eps8 and gelsolin have complementary roles in regulating the growth and stability of mechanosensory hair bundles of mammalian cochlear outer hair cells.
复制标题
DOI：
10.1371/journal.pone.0087331
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Brown SD
中科院分区：
文献类型：
--
作者：
Olt J;Mburu P;Johnson SL;Parker A;Kuhn S;Bowl M;Marcotti W;Brown SD
声传导依赖于位于耳蜗毛细胞顶面突起的毛状束上的机械敏感通道。毛束呈阶梯状结构，由一排排静纤毛组成，每个静纤毛都含有一个由排列紧密、极化均匀的肌动蛋白丝组成的核心。立体纤毛肌动蛋白核心的生长和维持是动态调节的。最近的研究表明，肌动蛋白结合蛋白凝溶胶蛋白在外毛细胞（OHC）的静纤毛中表达，并且在其缺失时，它们变得长而散乱。凝溶胶蛋白是静纤毛尖端的旋转支架蛋白复合物的一部分，它已被证明与其他肌动蛋白调节分子如Eps 8相互作用。在这里，我们研究了与凝溶胶蛋白的情况下，其可能的重叠作用与Eps 8的生理效应。我们发现，在相反的Eps 8，凝溶胶蛋白不影响机械电转导在不成熟的发展阶段。此外，从凝溶胶蛋白基因敲除小鼠的OHC能够成熟为功能齐全的感觉受体，判断正常的静息膜电位和基底外侧膜电流。在凝溶胶蛋白-Eps 8双敲除小鼠中的机电换能器电流显示出与在Eps 8的单突变体中观察到的类似的曲线。我们提出凝溶胶蛋白与Eps 8具有非重叠的作用。虽然Eps 8主要参与内毛细胞（IHC）和OHC中静纤毛的初始生长，但凝溶胶蛋白是听力发作后低频OHC的成熟毛束维持所需的。
Sound transduction depends upon mechanosensitive channels localized on the hair-like bundles that project from the apical surface of cochlear hair cells. Hair bundles show a stair-case structure composed of rows of stereocilia, and each stereocilium contains a core of tightly-packed and uniformly-polarized actin filaments. The growth and maintenance of the stereociliary actin core are dynamically regulated. Recently, it was shown that the actin-binding protein gelsolin is expressed in the stereocilia of outer hair cells (OHCs) and in its absence they become long and straggly. Gelsolin is part of a whirlin scaffolding protein complex at the stereocilia tip, which has been shown to interact with other actin regulatory molecules such as Eps8. Here we investigated the physiological effects associated with the absence of gelsolin and its possible overlapping role with Eps8. We found that, in contrast to Eps8, gelsolin does not affect mechanoelectrical transduction during immature stages of development. Moreover, OHCs from gelsolin knockout mice were able to mature into fully functional sensory receptors as judged by the normal resting membrane potential and basolateral membrane currents. Mechanoelectrical transducer current in gelsolin-Eps8 double knockout mice showed a profile similar to that observed in the single mutants for Eps8. We propose that gelsolin has a non-overlapping role with Eps8. While Eps8 is mainly involved in the initial growth of stereocilia in both inner hair cells (IHCs) and OHCs, gelsolin is required for the maintenance of mature hair bundles of low-frequency OHCs after the onset of hearing.
登录
查看更多内容
影响因子：
3.7
作者：
Mburu P;Romero MR;Hilton H;Parker A;Townsend S;Kikkawa Y;Brown SD
通讯作者：
Brown SD
影响因子：
4.5
作者：
Sekerková G;Richter CP;Bartles JR
通讯作者：
Bartles JR
DOI：
10.1523/jneurosci.2782-09.2009
发表时间：
2009-12-02
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Peng AW;Belyantseva IA;Hsu PD;Friedman TB;Heller S
通讯作者：
Heller S
DOI：
10.1098/rspb.1997.0087
发表时间：
1997-04-22
影响因子：
4.7
作者：
Geleoc, GSG;Lennan, GWT;Kros, CJ
通讯作者：
Kros, CJ
影响因子：
25
作者：
Kros, CJ;Marcotti, W;Steel, KP
通讯作者：
Steel, KP