Regulation of stereocilia length by myosin XVa and whirlin depends on the actin-regulatory protein Eps8.
Regulation of stereocilia length by myosin XVa and whirlin depends on the actin-regulatory protein Eps8.
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DOI：
10.1016/j.cub.2010.12.046
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发表时间：
2011-01-25
期刊：
影响因子：
9.2
通讯作者：
Kachar, Bechara
中科院分区：
文献类型：
--
作者：
Manor, Uri;Disanza, Andrea;Grati, M'Hamed;Andrade, Leonardo;Lin, Harrison;Di Fiore, Pier Paolo;Scita, Giorgio;Kachar, Bechara
肌球蛋白XVa（MyoXVa）及其货物旋转蛋白与耳聋和前庭功能障碍有关，并且已被证明定位于静纤毛尖端，并且对于这些肌动蛋白突起的伸长是必不可少的。鉴于whirlin没有已知的肌动蛋白调节活性，目前还不清楚这些蛋白质如何共同作用，以影响静纤毛长度。在这里，我们表明，肌动蛋白调节蛋白Eps8与MyoXVa相互作用，缺乏Eps8的小鼠显示短静纤毛与MyoXVa和whirlin缺陷小鼠相当。我们发现，Eps8未能积累在静纤毛的尖端在MyoXVa的情况下，MyoXVa的过度表达的结果在静纤毛的伸长以及增加的积累Eps8在静纤毛尖端，和MyoXVa缺陷的毛细胞中的外源性表达的MyoXVa拯救Eps8尖端定位。我们发现Eps8也与whirlin相互作用，并且在whirlin缺陷小鼠中，Eps8和MyoXVa在静纤毛尖端的表达减少。我们的结论是MyoXVa，whirlin，和Eps8的静纤毛尖端复杂的Eps8是一个中央肌动蛋白调节元件的静纤毛肌动蛋白核心的伸长的组成部分。
Myosin XVa (MyoXVa) and its cargo whirlin are implicated in deafness and vestibular dysfunction and have been shown to localize at stereocilia tips and to be essential for the elongation of these actin protrusions. Given that whirlin has no known actin-regulatory activity, it remains unclear how these proteins work together to influence stereocilia length. Here we show that the actin-regulatory protein Eps8 interacts with MyoXVa and that mice lacking Eps8 show short stereocilia comparable to MyoXVa and whirlin deficient mice. We show that Eps8 fails to accumulate at the tips of stereocilia in the absence of MyoXVa, that overexpression of MyoXVa results in both elongation of stereocilia as well as increased accumulation of Eps8 at stereocilia tips, and that the exogenous expression of MyoXVa in MyoXVa-deficient hair cells rescues Eps8 tip-localization. We find that Eps8 also interacts with whirlin and that the expression of both Eps8 and MyoXVa at stereocilia tips is reduced in whirlin-deficient mice. We conclude that MyoXVa, whirlin, and Eps8 are integral components of the stereocilia tip complex where Eps8 is a central actin-regulatory element for elongation of the stereocilia actin core.
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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：
56.9
作者：
Wang, AH;Liang, Y;Friedman, TB
通讯作者：
Friedman, TB
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
影响因子：
30.8
作者：
Mburu, P;Mustapha, M;Brown, SDM
通讯作者：
Brown, SDM
DOI：
10.1073/pnas.0600923103
发表时间：
2006-07-18
影响因子：
11.1
作者：
Mburu, Philomena;Kikkawa, Yoshiaki;Brown, Steve D. M.
通讯作者：
Brown, Steve D. M.