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Mechanotransduction-Dependent Control of Stereocilia Dimensions and Row Identity in Inner Hair Cells.
Current Biology ( IF 9.2 ) Pub Date : 2020-01-02 , DOI: 10.1016/j.cub.2019.11.076
Jocelyn F Krey 1 , Paroma Chatterjee 1 , Rachel A Dumont 1 , Mary O'Sullivan 2 , Dongseok Choi 3 , Jonathan E Bird 4 , Peter G Barr-Gillespie 5
Affiliation  

Actin-rich structures, like stereocilia and microvilli, are assembled with precise control of length, diameter, and relative spacing. By quantifying actin-core dimensions of stereocilia from phalloidin-labeled mouse cochleas, we demonstrated that inner hair cell stereocilia developed in specific stages, where a widening phase is sandwiched between two lengthening phases. Moreover, widening of the second-tallest stereocilia rank (row 2) occurred simultaneously with the appearance of mechanotransduction. Correspondingly, Tmc1KO/KO;Tmc2KO/KO or TmieKO/KO hair cells, which lack transduction, have significantly altered stereocilia lengths and diameters, including a narrowed row 2. EPS8 and the short splice isoform of MYO15A, identity markers for mature row 1 (the tallest row), lost their row exclusivity in transduction mutants. GNAI3, another member of the mature row 1 complex, accumulated at mutant row 1 tips at considerably lower levels than in wild-type bundles. Alterations in stereocilia dimensions and in EPS8 distribution seen in transduction mutants were mimicked by block of transduction channels of cochlear explants in culture. In addition, proteins normally concentrated at mature row 2 tips were also distributed differently in transduction mutants; the heterodimeric capping protein subunit CAPZB and its partner TWF2 never concentrated at row 2 tips like they do in wild-type bundles. The altered distribution of marker proteins in transduction mutants was accompanied by increased variability in stereocilia length. Transduction channels thus specify and maintain row identity, control addition of new actin filaments to increase stereocilia diameter, and coordinate stereocilia height within rows.

中文翻译:

机械传递依赖控制的内毛细胞中的毛细血管尺寸和行身份。

富含肌动蛋白的结构(如立体纤毛和微绒毛)可以精确控制长度,直径和相对间距进行组装。通过量化来自鬼笔环肽标记的小鼠耳蜗的立体纤毛的肌动蛋白核心尺寸,我们证明了内部毛细胞立体纤毛在特定阶段发育,其中一个扩展阶段夹在两个延长阶段之间。此外,第二高的立体纤毛等级(第2行)的扩大与机械转导的出现同时发生。相应地,缺乏转导的Tmc1KO / KO; Tmc2KO / KO或TmieKO / KO毛细胞具有明显改变的纤毛长度和直径,包括变窄的第2行。EPS8和MYO15A的短剪接同工型,是成熟第1行的同一标记(最高的行),在转导突变体中失去了行的排他性。GNAI3,成熟的第1行复合体的另一成员,在突变的第1行尖端积累的水平比野生型束中低得多。在转导突变体中看到的立体纤毛尺寸和EPS8分布的变化被培养中人工耳蜗外植体的转导通道阻滞所模仿。另外,通常浓缩在成熟的第2行末端的蛋白质在转导突变体中也有不同的分布;异二聚体封端蛋白CAPZB亚基及其伴侣TWF2从未像在野生型束中那样集中在第2行末端。标记蛋白在转导突变体中分布的改变伴随着纤毛长度的变异性增加。因此,转导通道可指定并维持行身份,控制新肌动蛋白丝的添加以增加纤毛直径,
更新日期:2020-01-02
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