POSH Localizes Activated Rac1 to Control the Formation of Cytoplasmic Dilation of the Leading Process and Neuronal Migration
POSH Localizes Activated Rac1 to Control the Formation of Cytoplasmic Dilation of the Leading Process and Neuronal Migration
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POSH 定位激活的 Rac1 来控制前导过程细胞质扩张和神经元迁移的形成
DOI：
10.1016/j.celrep.2012.08.007
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发表时间：
2012-09-01
期刊：
影响因子：
8.8
通讯作者：
Xu, Zhiheng
中科院分区：
文献类型：
--
作者：
Yang, Tao;Sun, Yiming;Xu, Zhiheng
近端细胞质扩张的形成在迁移的新皮层神经元的主导过程（PCDLP）是至关重要的染色体易位和神经元迁移，过程中需要精心协调的F-肌动蛋白动力学，中心体运动，核分裂。然而，潜在的分子机制仍然知之甚少。在这里，我们表明，Rac 1相互作用的支架蛋白POSH是必不可少的神经元迁移在体内。我们证明，POSH是集中在PCDLP和敲低POSH损害PCDLP的形成，中心体易位，核分裂。此外，POSH与F-actin和Rac 1的活化形式共定位。POSH的敲低损害F-肌动蛋白组装并使活化的Rac 1离域。Rac 1活性的干扰也会破坏F-肌动蛋白组装和PCDLP形成，并扰乱神经元迁移。因此，我们已经发现了一种机制，POSH调节激活的Rac 1和F-actin组件的本地化，以控制PCDLP的形成和随后的迁移神经元的染色体易位。
The formation of proximal cytoplasmic dilation in the leading process (PCDLP) of migratory neocortical neurons is crucial for somal translocation and neuronal migration, processes that require the elaborate coordination of F-actin dynamics, centrosomal movement, and nucleokinesis. However, the underlying molecular mechanisms remain poorly understood. Here, we show that the Rac1-interacting scaffold protein POSH is essential for neuronal migration in vivo. We demonstrate that POSH is concentrated in the PCDLP and that knockdown of POSH impairs PCDLP formation, centrosome translocation, and nucleokinesis. Furthermore, POSH colocalizes with F-actin and the activated form of Rac1. Knockdown of POSH impairs F-actin assembly and delocalizes activated Rac1. Interference of Rac1 activity also disrupts F-actin assembly and PCDLP formation and perturbs neuronal migration. Thus, we have uncovered a mechanism by which POSH regulates the localization of activated Rac1 and F-actin assembly to control PCDLP formation and subsequent somal translocation of migratory neurons.