Both the establishment and maintenance of neuronal polarity require the activity of protein kinase D in the Golgi apparatus
Both the establishment and maintenance of neuronal polarity require the activity of protein kinase D in the Golgi apparatus
复制标题
神经元极性的建立和维持都需要高尔基体中蛋白激酶D的活性
DOI：
10.1523/jneurosci.1291-08.2008
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发表时间：
2008-08-27
影响因子：
5.3
通讯作者：
Wang, Yun
中科院分区：
文献类型：
--
作者：
Yin, Dong-Min;Huang, Yan-Hua;Wang, Yun
神经元极化需要膜转运和细胞骨架动力学的协调调节。一些信号蛋白通过调节神经突起中的细胞骨架动力学参与神经元的极化。然而，对神经元胞体中调节极化膜运输和神经元极化的信号蛋白知之甚少。蛋白激酶D(PKD)是一类丝氨酸/苏氨酸特异的蛋白激酶家族，在调节高尔基体动力学和膜转运中起重要作用。在这里，我们展示了PKD家族的两个成员，PKD1和PKD2，对于神经元极性的建立和维持是必不可少的。抑制、显性负性和短干扰RNA使PKD功能丧失，破坏极化的膜转运，诱导多个轴突的形成。PKD功能的获得可以挽救细胞松弛素D引起的极化膜转运和神经元极性的破坏，从而导致F-肌动蛋白解聚。PKD1和PKD2也被发现参与神经元极性的维持，在PKD抑制时，先前存在的树突转化为轴突就证明了这一点。与其他极性蛋白不同，PKD不与神经突起中的细胞骨架相互作用。相反，PKD通过其在高尔基体中的活动来调节神经元的极性。这些数据揭示了高尔基体中调节神经元极性的一种新机制。
Neuronal polarization requires coordinated regulation of membrane trafficking and cytoskeletal dynamics. Several signaling proteins are involved in neuronal polarization via modulation of cytoskeletal dynamics in neurites. However, very little is known about signaling proteins in the neuronal soma, which regulate polarized membrane trafficking and neuronal polarization. Protein kinase D (PKD) constitutes a family of serine/threonine-specific protein kinases and is important in regulating Golgi dynamics and membrane trafficking. Here, we show that two members of the PKD family, PKD1 and PKD2, are essential for the establishment and maintenance of neuronal polarity. Loss of function of PKD with inhibitor, dominant negative, and short interfering RNA disrupts polarized membrane trafficking and induces multiple axon formation. Gain of function of PKD can rescue the disruption of polarized membrane trafficking and neuronal polarity caused by cytochalasin D, which results in F-actin depolymerization. PKD1 and PKD2 are also found to be involved in the maintenance of neuronal polarity, as evidenced by the conversion of preexisting dendrites into axons on PKD inhibition. Unlike other polarity proteins, PKD does not interact with the cytoskeleton in neurites. Instead, PKD regulates neuronal polarity through its activity in the Golgi apparatus. These data reveal a novel mechanism regulating neuronal polarity in the Golgi apparatus.