Akt-independent GSK3 inactivation downstream of PI3K signaling regulates mammalian axon regeneration.
Akt-independent GSK3 inactivation downstream of PI3K signaling regulates mammalian axon regeneration.
复制标题
DOI：
10.1016/j.bbrc.2013.12.037
复制
发表时间：
2014-01-10
影响因子：
3.1
通讯作者：
Zhou, Feng-Quan
中科院分区：
文献类型：
--
作者：
Zhang, Bo-Yin;Saijilafu;Liu, Chang-Mei;Wang, Rui-Ying;Zhu, Qingsan;Jiao, Zhongxian;Zhou, Feng-Quan
糖原合成酶激酶3（GSK 3）的失活已被证明在发育和再生过程中介导轴突生长。众所周知，激酶Akt对GSK 3的磷酸化是GSK 3失活的主要机制。然而，这种GSK 3失活的调节机制是否在神经元中用于控制轴突生长尚未直接研究。在这里，通过使用GSK 3突变小鼠，其中GSK 3是不敏感的Akt介导的失活，我们表明，感觉轴突再生正常，在体外和体内外周轴突切断后。我们还发现突变小鼠感觉神经元中的GSK 3在外周轴突切断后仍然失活，这种失活是感觉轴突再生所必需的。最后，我们提供的证据表明，GSK 3活性是负调控的PI 3 K信号在突变小鼠外周轴突切断后，和PI 3 K-GSK 3通路的功能所需的感觉轴突再生。总之，这些结果表明，在响应外周神经损伤GSK 3失活，调节的替代机制独立的Akt介导的磷酸化，控制感觉轴突再生。
Inactivation of glycogen synthase kinase 3 (GSK3) has been shown to mediate axon growth during development and regeneration. Phosphorylation of GSK3 by the kinase Akt is well known to be the major mechanism by which GSK3 is inactivated. However, whether such regulatory mechanism of GSK3 inactivation is used in neurons to control axon growth has not been directly studied. Here by using GSK3 mutant mice, in which GSK3 is insensitive to Akt-mediated inactivation, we show that sensory axons regenerate normally in vitro and in vivo after peripheral axotomy. We also find that GSK3 in sensory neurons of the mutant mice is still inactivated in response to peripheral axotomy and such inactivation is required for sensory axon regeneration. Lastly, we provide evidence that GSK3 activity is negatively regulated by PI3K signaling in the mutant mice upon peripheral axotomy, and the PI3K-GSK3 pathway is functionally required for sensory axon regeneration. Together, these results indicate that in response to peripheral nerve injury GSK3 inactivation, regulated by an alternative mechanism independent of Akt-mediated phosphorylation, controls sensory axon regeneration.
登录
查看更多内容
影响因子：
34.7
作者：
Hur, Eun-Mi;Zhou, Feng-Quan
通讯作者：
Zhou, Feng-Quan
影响因子：
64.5
作者：
Yoshimura, T;Kawano, Y;Kaibuchi, K
通讯作者：
Kaibuchi, K
影响因子：
10.5
作者：
Hur, Eun-Mi;Saijilafu;Zhou, Feng-Quan
通讯作者：
Zhou, Feng-Quan
影响因子：
10.5
作者：
Liu, Chang-Mei;Wang, Rui-Ying;Zhou, Feng-Quan
通讯作者：
Zhou, Feng-Quan
影响因子：
16.6
作者：
Saijilafu;Hur, Eun-Mi;Liu, Chang-Mei;Jiao, Zhongxian;Xu, Wen-Lin;Zhou, Feng-Quan
通讯作者：
Zhou, Feng-Quan