Tsai N-P, Tsui Y-C, Wei L-N
Department of Pharmacology, University of Minnesota Medical School, 6-120 Jackson Hall, 321 Church Street Southeast, Minneapolis, MN 55455, USA.
Neuroscience. 2009 Mar 17;159(2):647-56. doi: 10.1016/j.neuroscience.2008.12.053. Epub 2009 Jan 3.
Mobilization and translation of mRNAs, two important events believed to involve stress granules (SGs), in neurons are important for their survival and activities. However, the formation and disassembly of SGs in neurons remains unclear. By using an arsenite-induced neuronal stress model of rat primary spinal cord neuron cultures, we demonstrate the formation of SGs that contain common SG components and RNAs in both stressed neuronal cell bodies and their neurites. By employing small interfering RNA (siRNA) knockdown, we discovered that dynein motor subunit localizes in SG, and is important for SG assembly in neurons. Under stress, dynein motor subunit also facilitates translational repression and enhances the formation and integrity of SG in neurons. By blocking the energy source of dynein motor, both the formation and disassembly of SG are attenuated. These findings demonstrate, for the first time, that dynein motor complex plays a critical role in the dynamics of neuronal SGs, as well as translation of certain mRNAs.
信使核糖核酸(mRNA)的动员与翻译是神经元生存和活动的重要过程,这两个重要事件被认为与应激颗粒(SGs)有关。然而,神经元中SGs的形成和分解仍不清楚。通过使用亚砷酸盐诱导的大鼠原代脊髓神经元培养物的神经元应激模型,我们证明了在应激的神经元细胞体及其神经突中形成了含有常见SG成分和RNA的SGs。通过采用小干扰RNA(siRNA)敲低技术,我们发现动力蛋白运动亚基定位于SGs,并且对神经元中SGs的组装很重要。在应激条件下,动力蛋白运动亚基还促进翻译抑制,并增强神经元中SGs的形成和完整性。通过阻断动力蛋白运动的能量来源,SGs的形成和分解均减弱。这些发现首次证明,动力蛋白运动复合体在神经元SGs的动态变化以及某些mRNA的翻译中起关键作用。