Dynein motor contributes to stress granule dynamics in primary neurons.

Dynein motor contributes to stress granule dynamics in primary neurons.
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DOI:
10.1016/j.neuroscience.2008.12.053
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发表时间:
2009-03-17
期刊:
影响因子:
3.3
通讯作者:
Wei LN
Wei LN
中科院分区:
医学3区
文献类型:
--
作者:
Tsai NP;Tsui YC;Wei LN

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应激颗粒(stress granules,SGs)参与了神经元内mRNA的动员和翻译,这两个重要事件对神经元的生存和活动具有重要意义。然而,SGs在神经元中的形成和分解仍不清楚。通过使用砷诱导的神经元应力模型的原代脊髓神经元培养物,我们证明了SG的形成,包含共同的SG组件和RNA在这两个强调神经元细胞体和它们的神经突。通过siRNA敲除,我们发现动力蛋白运动亚基定位于SG,并且对于神经元中SG的组装是重要的。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SG的形成和完整性。通过阻断动力蛋白马达的能量来源,SG的形成和分解都被减弱。这些发现首次证明,动力蛋白运动复合体在神经元SGs的动力学以及某些mRNA的翻译中起着关键作用。
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 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 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.
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