Yin Dong-Min, Huang Yan-Hua, Zhu Yan-Bing, Wang Yun
Neuroscience Research Institute and Department of Neurobiology, Key Laboratory for Neuroscience of Ministry of Education and Health, Peking University, Beijing 100083, People's Republic of China.
J Neurosci. 2008 Aug 27;28(35):8832-43. doi: 10.1523/JNEUROSCI.1291-08.2008.
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.
神经元极化需要膜运输和细胞骨架动力学的协调调节。几种信号蛋白通过调节神经突中的细胞骨架动力学参与神经元极化。然而，关于神经元胞体中调节极化膜运输和神经元极化的信号蛋白，我们所知甚少。蛋白激酶D（PKD）构成一个丝氨酸/苏氨酸特异性蛋白激酶家族，在调节高尔基体动力学和膜运输中起重要作用。在这里，我们表明PKD家族的两个成员PKD1和PKD2对于神经元极性的建立和维持至关重要。用抑制剂、显性负性和短发夹RNA抑制PKD的功能会破坏极化膜运输并诱导多个轴突形成。PKD功能的增强可以挽救由细胞松弛素D导致的F-肌动蛋白解聚所引起的极化膜运输和神经元极性的破坏。PKD1和PKD2也被发现参与神经元极性的维持，PKD抑制后，已有的树突会转变为轴突，这证明了这一点。与其他极性蛋白不同，PKD在神经突中不与细胞骨架相互作用。相反，PKD通过其在高尔基体中的活性来调节神经元极性。这些数据揭示了一种在高尔基体中调节神经元极性的新机制。
