Ezrin mediates neuritogenesis via down-regulation of RhoA activity in cultured cortical neurons.
Ezrin mediates neuritogenesis via down-regulation of RhoA activity in cultured cortical neurons.
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DOI：
10.1371/journal.pone.0105435
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Asano S
中科院分区：
文献类型：
--
作者：
Matsumoto Y;Inden M;Tamura A;Hatano R;Tsukita S;Asano S
神经元的形态发生与神经元的功能和发育以及细胞骨架组织的重排有关。Ezrin是Ezrin/Radixin/Moesin（ERM）蛋白的一个成员，连接细胞膜蛋白和肌动蛋白细胞骨架，参与细胞功能和形态的维持。在培养的海马神经元中，抑制radixin和膜突蛋白显示生长锥形态和神经突延伸的缺陷。使用siRNA下调ezrin导致netrin-1诱导的培养皮层神经元轴突生长受损。然而，ezrin在培养的神经元的神经元形态发生中的作用一直知之甚少。在这份报告中，我们进行了详细的研究ezrin在培养的皮质神经元的ezrin敲除（Vil 2kd/kd）小鼠胚胎，显示了非常少量的ezrin表达相比，野生型（Vil 2 +/+）神经元制备的作用。Ezrin主要表达于培养的皮层神经元胞体。我们证明，从Vil 2kd/kd小鼠胚胎制备的培养皮层神经元表现出损害的轴突发生。此外，我们观察到增加的RhoA活性和肌球蛋白轻链2（MLC 2）的磷酸化，作为RhoA在Vil 2kd/kd神经元的下游效应。此外，Rho激酶和肌球蛋白II的抑制挽救了Vil 2kd/kd神经元的轴突发生的损伤。这些数据表明ezrin通过下调RhoA活性在培养的皮层神经元的轴突发生中具有新的作用。
Neuronal morphogenesis is implicated in neuronal function and development with rearrangement of cytoskeletal organization. Ezrin, a member of Ezrin/Radixin/Moesin (ERM) proteins links between membrane proteins and actin cytoskeleton, and contributes to maintenance of cellular function and morphology. In cultured hippocampal neurons, suppression of both radixin and moesin showed deficits in growth cone morphology and neurite extensions. Down-regulation of ezrin using siRNA caused impairment of netrin-1-induced axon outgrowth in cultured cortical neurons. However, roles of ezrin in the neuronal morphogenesis of the cultured neurons have been poorly understood. In this report, we performed detailed studies on the roles of ezrin in the cultured cortical neurons prepared from the ezrin knockdown (Vil2kd/kd) mice embryo that showed a very small amount of ezrin expression compared with the wild-type (Vil2+/+) neurons. Ezrin was mainly expressed in cell body in the cultured cortical neurons. We demonstrated that the cultured cortical neurons prepared from the Vil2kd/kd mice embryo exhibited impairment of neuritogenesis. Moreover, we observed increased RhoA activity and phosphorylation of myosin light chain 2 (MLC2), as a downstream effector of RhoA in the Vil2kd/kd neurons. In addition, inhibition of Rho kinase and myosin II rescued the impairment of neuritogenesis in the Vil2kd/kd neurons. These data altogether suggest a novel role of ezrin in the neuritogenesis of the cultured cortical neurons through down-regulation of RhoA activity.
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DOI：
10.1083/jcb.109.4.1621
发表时间：
1989-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Goslin K;Birgbauer E;Banker G;Solomon F
通讯作者：
Solomon F
影响因子：
3.3
作者：
Antoine-Bertrand J;Ghogha A;Luangrath V;Bedford FK;Lamarche-Vane N
通讯作者：
Lamarche-Vane N
影响因子：
25
作者：
Krey, Jocelyn F.;Pasca, Sergiu P.;Shcheglovitov, Aleksandr;Yazawa, Masayuki;Schwemberger, Rachel;Rasmusson, Randall;Dolmetsch, Ricardo E.
通讯作者：
Dolmetsch, Ricardo E.
影响因子：
3.5
作者：
Grönholm, M;Teesalu, T;Carpén, O
通讯作者：
Carpén, O
影响因子：
12.7
作者：
Johnson, MW;Miyata, H;Vinters, HV
通讯作者：
Vinters, HV