Actin at stereocilia tips is regulated by mechanotransduction and ADF/cofilin.
Actin at stereocilia tips is regulated by mechanotransduction and ADF/cofilin.
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DOI：
10.1016/j.cub.2020.12.006
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发表时间：
2021-03-22
期刊：
影响因子：
--
通讯作者：
Perrin BJ
中科院分区：
文献类型：
--
作者：
McGrath J;Tung CY;Liao X;Belyantseva IA;Roy P;Chakraborty O;Li J;Berbari NF;Faaborg-Andersen CC;Barzik M;Bird JE;Zhao B;Balakrishnan L;Friedman TB;Perrin BJ
听觉感觉细胞上的立体纤毛是基于肌动蛋白的突起，它将声音机械地转化为电信号。这些立体纤毛排列成一束，有三排长度增加，形成一个阶梯状的形态，这是听力所必需的。在较短的行中，而不是最高的行中，立体纤毛是机械传导的，因为它们的尖端有力敏感通道。在小鼠出生后发育过程中机械转导的开始细化了纤毛的长度和宽度。然而，目前尚不清楚肌动蛋白在纤毛束最高行和较短的机械传导行中是如何被不同的纤毛调控的。这里我们显示肌动蛋白周转在机械转导立体纤毛的尖端在束成熟过程中增加。相应地，从出生到出生后第6天，与最高排的非机械转导立体纤毛相比，这些立体纤毛具有越来越多的可用肌动蛋白倒钩末端，在那里单体可以很容易地添加或丢失。可用的倒刺末端的增加取决于机械转导和MYO15或EPS8，这是最高排直立纤毛的正常规格和伸长所必需的。我们还发现f -肌动蛋白切断蛋白ADF和cofilin-1的缺失降低了直立纤毛尖端的倒刺末端可用性。这些蛋白在机械转导立体纤毛尖端富集，它们的定位受到机械转导、MYO15或EPS8缺失的干扰。最后，Adf和Cfl1突变体的纤毛长度和宽度失调。综上所述，这些数据表明肌动蛋白在机械转导的作用下被重塑，很可能是通过一种切断机制。
Stereocilia on auditory sensory cells are actin-based protrusions that mechanotransduce sound into an electrical signal. These stereocilia are arranged into a bundle with three rows of increasing length to form a staircase-like morphology that is required for hearing. Stereocilia in the shorter rows, but not the tallest row, are mechanotransducing because they have force sensitive channels localized at their tips. The onset of mechanotransduction during mouse postnatal development refines stereocilia length and width. However, it is unclear how actin is differentially regulated between stereocilia in the tallest row of the bundle and the shorter, mechanotransducing rows. Here we show actin turnover is increased at the tips of mechanotransducing stereocilia during bundle maturation. Correspondingly, from birth to postnatal day 6, these stereocilia had increasing amounts of available actin barbed ends, where monomers can be added or lost readily, as compared to the non-mechanotransducing stereocilia in the tallest row. The increase in available barbed ends depended on both mechanotransduction and MYO15 or EPS8, which are required for the normal specification and elongation of the tallest row of stereocilia. We also found that loss of the F-actin severing proteins ADF and cofilin-1 decreased barbed end availability at stereocilia tips. These proteins enriched at mechanotransducing stereocilia tips and their localization was perturbed by the loss of mechanotransduction, MYO15, or EPS8. Finally, stereocilia lengths and widths were dysregulated in Adf and Cfl1 mutants. Together, these data show that actin is remodeled, likely by a severing mechanism, in response to mechanotransduction.
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DOI：
10.1083/jcb.201704171
发表时间：
2017-11-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Avenarius MR;Krey JF;Dumont RA;Morgan CP;Benson CB;Vijayakumar S;Cunningham CL;Scheffer DI;Corey DP;Müller U;Jones SM;Barr-Gillespie PG
通讯作者：
Barr-Gillespie PG
影响因子：
5.6
作者：
Hilton DM;Aguilar RM;Johnston AB;Goode BL
通讯作者：
Goode BL
影响因子：
9.8
作者：
Hertzog M;Milanesi F;Hazelwood L;Disanza A;Liu H;Perlade E;Malabarba MG;Pasqualato S;Maiolica A;Confalonieri S;Le Clainche C;Offenhauser N;Block J;Rottner K;Di Fiore PP;Carlier MF;Volkmann N;Hanein D;Scita G
通讯作者：
Scita G
影响因子：
16.6
作者：
Corns LF;Johnson SL;Roberts T;Ranatunga KM;Hendry A;Ceriani F;Safieddine S;Steel KP;Forge A;Petit C;Furness DN;Kros CJ;Marcotti W
通讯作者：
Marcotti W
DOI：
10.1073/pnas.2334417100
发表时间：
2003-11-25
影响因子：
11.1
作者：
Belyantseva, IA;Boger, ET;Friedman, TB
通讯作者：
Friedman, TB