Inactivation of Cyclin-Dependent Kinase 5 in Hair Cells Causes Hearing Loss in Mice
Inactivation of Cyclin-Dependent Kinase 5 in Hair Cells Causes Hearing Loss in Mice
复制标题
毛细胞中细胞周期蛋白依赖性激酶 5 失活导致小鼠听力损失
DOI：
10.3389/fnmol.2018.00461
复制
发表时间：
2018-12
影响因子：
4.8
通讯作者：
Xu Zhigang
中科院分区：
文献类型：
--
作者：
Zhai Xiaoyan;Liu Chengcheng;Zhao Bin;Wang Yanfei;Xu Zhigang
细胞周期蛋白依赖性激酶5（CDK 5）在包括神经元在内的有丝分裂后细胞中大量表达。CDK 5参与细胞骨架动力学、信号转导、基因表达、细胞存活等多种细胞事件。在这里，我们表明，CDK 5在小鼠耳蜗毛细胞中表达，CDK 5在毛细胞中的失活导致小鼠听力损失。CDK 5失活对耳蜗毛细胞静纤毛的发育没有影响。然而，它会影响静纤毛的维持，导致静纤毛紊乱，最终导致静纤毛丧失。一致地，CDK 5失活显著增加毛细胞损失。尽管CDK 5已被证明在突触发育和/或功能中起重要作用，但CDK 5失活并不影响耳蜗毛细胞带状突触的形成。进一步的研究表明，CDK 5失活导致ERM（ezrin，radixin和moesin）蛋白磷酸化减少，这可能导致静纤毛缺陷。总之，我们的数据表明，CDK 5在听毛细胞中起着关键作用，CDK 5失活导致小鼠听力损失。
Cyclin-dependent kinase 5 (CDK5) is abundantly expressed in post-mitotic cells including neurons. It is involved in multiple cellular events, such as cytoskeletal dynamics, signaling cascades, gene expression, and cell survival, et al. Dysfunction of CDK5 has been associated with a number of neurological disorders. Here we show that CDK5 is expressed in mouse cochlear hair cells, and CDK5 inactivation in hair cells causes hearing loss in mice. CDK5 inactivation has no effect on stereocilia development in the cochlear hair cells. However, it affects stereocilia maintenance, resulting in stereocilia disorganization and eventually stereocilia loss. Consistently, hair cell loss was significantly elevated by CDK5 inactivation. Despite that CDK5 has been shown to play important roles in synapse development and/or function, CDK5 inactivation does not affect the formation of ribbon synapses of cochlear hair cells. Further investigation showed that CDK5 inactivation causes reduced phosphorylation of ERM (ezrin, radixin, and moesin) proteins, which might contribute to the stereocilia deficits. Taken together, our data suggest that CDK5 plays pivotal roles in auditory hair cells, and CDK5 inactivation causes hearing loss in mice.
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DOI：
10.1111/j.1432-1033.1997.t01-2-00527.x
发表时间：
1997-01-15
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Meijer, L;Borgne, A;Moulinoux, JP
通讯作者：
Moulinoux, JP
影响因子：
64.8
作者：
Banks, Alexander S.;McAllister, Fiona E.;Camporez, Joao Paulo G.;Zushin, Peter-James H.;Jurczak, Michael J.;Laznik-Bogoslavski, Dina;Shulman, Gerald I.;Gygi, Steven P.;Spiegelman, Bruce M.
通讯作者：
Spiegelman, Bruce M.
影响因子：
8
作者：
NavaneethaKrishnan S;Rosales JL;Lee KY
通讯作者：
Lee KY
DOI：
10.1152/ajpcell.00339.2011
发表时间：
2012-03
期刊：
American journal of physiology. Cell physiology
影响因子：
--
作者：
J. Bai;Alexei A. Surguchev;Powrnima Joshi;Liza Gross;D. Navaratnam
通讯作者：
J. Bai;Alexei A. Surguchev;Powrnima Joshi;Liza Gross;D. Navaratnam
影响因子：
16.2
作者：
Lin, WC;Dominguez, B;Lee, KF
通讯作者：
Lee, KF