hnRNP Q Regulates Cdc42-Mediated Neuronal Morphogenesis
hnRNP Q Regulates Cdc42-Mediated Neuronal Morphogenesis
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DOI：
10.1128/mcb.06550-11
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发表时间：
2012-06-01
影响因子：
5.3
通讯作者：
Tarn, Woan-Yuh
中科院分区：
文献类型：
--
作者：
Chen, Hung-Hsi;Yu, Hsin-I;Tarn, Woan-Yuh
RNA结合蛋白hnRNP Q与神经元mRNA代谢有关。在这里，我们发现，敲低hnRNP Q增加了培养的大鼠皮层神经元的神经突起的复杂性，并诱导小鼠神经母细胞瘤细胞的丝状伪足形成。hnRNP Q-耗尽细胞中hnRNP Q 1的重新表达废除了神经突的形态变化，表明hnRNP Q 1在神经元形态发生中的特定作用。一个搜索的mRNA目标的hnRNP Q1确定功能连贯套的mRNA编码因子参与细胞信号传导或细胞骨架调控，并确定其首选的结合序列。我们证明，hnRNP Q1绑定到一组确定的mRNA编码的肌动蛋白成核促进Cdc 42/N-WASP/Arp 2/3复合物的组件，并在颗粒中与Cdc 42 mRNA共定位的一部分。利用亚细胞分级分离和免疫荧光技术，我们发现hnRNP Q基因敲低后，神经突中的一些mRNA水平降低，其编码的蛋白质从神经突尖端不同程度地重新分布到索马中。Cdc 42或N-WASP显性负突变体的过表达损害了hnRNP Q耗竭诱导的神经突复杂性。总之，我们的研究结果表明，hnRNP Q1可能参与定位的mRNA编码Cdc 42信号转导因子在神经突，从而可以调节肌动蛋白动力学和控制神经元形态发生。
The RNA-binding protein hnRNP Q has been implicated in neuronal mRNA metabolism. Here, we show that knockdown of hnRNP Q increased neurite complexity in cultured rat cortical neurons and induced filopodium formation in mouse neuroblastoma cells. Reexpression of hnRNP Q1 in hnRNP Q-depleted cells abrogated the morphological changes of neurites, indicating a specific role for hnRNP Q1 in neuronal morphogenesis. A search for mRNA targets of hnRNP Q1 identified functionally coherent sets of mRNAs encoding factors involved in cellular signaling or cytoskeletal regulation and determined its preferred binding sequences. We demonstrated that hnRNP Q1 bound to a set of identified mRNAs encoding the components of the actin nucleation-promoting Cdc42/N-WASP/Arp2/3 complex and was in part colocalized with Cdc42 mRNA in granules. Using subcellular fractionation and immunofiuorescence, we showed that knockdown of hnRNP Q reduced the level of some of those mRNAs in neurites and redistributed their encoded proteins from neurite tips to soma to different extents. Overexpression of dominant negative mutants of Cdc42 or N-WASP compromised hnRNP Q depletion-induced neurite complexity. Together, our results suggest that hnRNP Q1 may participate in localization of mRNAs encoding Cdc42 signaling factors in neurites, and thereby may regulate actin dynamics and control neuronal morphogenesis.