Activity-dependent expression of RNA binding protein HuD and its association with mRNAs in neurons
Activity-dependent expression of RNA binding protein HuD and its association with mRNAs in neurons
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DOI：
10.4161/rna.5.3.6782
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发表时间：
2008-07-01
期刊：
影响因子：
4.1
通讯作者：
Keene, Jack D.
中科院分区：
文献类型：
--
作者：
Tiruchinapalli, Dhanrajan M.;Ehlers, Michael D.;Keene, Jack D.
树突状细胞内RNA结合蛋白的运输是一个重要的转录后过程，参与突触可塑性的调节。例如，HuD RBP结合立即早期基因（IEG）转录物的3'非翻译区（3' UTR）中的富含AU的元件（战神），其蛋白质产物直接影响突触可塑性。然而，HuD RBP和相关mRNA的亚细胞定位尚未在神经元刺激后进行研究。免疫荧光分析揭示了KCl刺激后HuD RBP在海马神经元中的活性依赖性树突状定位，而免疫沉淀证明了HuD RBP与编码neuritin、Homerla、GAP-43、Neuroligins、Verge和CAMK II α的神经元mRNA的关联。HuD的活性依赖性表达涉及NMDAR的激活，因为NMDA受体I敲除小鼠（Nr 1（neo-/-））显示HuD表达降低。此外，HuD相关转录物的翻译调节通过其与多聚腺苷酸结合蛋白（PABP）以及帽结合蛋白（eIF 4 E）的共定位来提出。我们认为HuD RBP对神经元mRNA的转录后调控介导了突触可塑性中蛋白质合成依赖性的变化。
The dendritic trafficking of RNA binding proteins (RBPs) is an important posttranscriptional process involved in the regulation of synaptic plasticity. For example, HuD RBP binds to AU-rich elements (AREs) in the 3' untranslated regions (3'UTR) of immediate-early gene (IEG) transcripts, whose protein products directly affect synaptic plasticity. However, the subcellular localization of HuD RBPs and associated mRNAs has not been investigated following neuronal stimulation. Immunofluorescence analysis revealed activity-dependent dendritic localization of HuD RBPs following KCl stimulation in hippocampal neurons, while immunoprecipitation demonstrated the association of HuD RBP with neuronal mRNAs encoding neuritin, Homerla, GAP-43, Neuroligins, Verge and CAMKII alpha. Activity-dependent expression of HuD involves activation of NMDAR as NMDA receptor I knockout mice (Nr1(neo-/-)) exhibited decreased expression of HuD. Moreover, translational regulation of HuD-associated transcripts was suggested by its co-localization with poly-A-binding protein (PABP) as well as the cap-binding protein (eIF4E). We propose that post-transcriptional regulation of neuronal mRNAs by HuD RBPs mediates protein synthesis-dependent changes in synaptic plasticity.