c-Jun N-Terminal Kinase Phosphorylation of Heterogeneous Nuclear Ribonucleoprotein K Regulates Vertebrate Axon Outgrowth via a Posttranscriptional Mechanism
c-Jun N-Terminal Kinase Phosphorylation of Heterogeneous Nuclear Ribonucleoprotein K Regulates Vertebrate Axon Outgrowth via a Posttranscriptional Mechanism
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DOI：
10.1523/jneurosci.4821-12.2013
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发表时间：
2013-09-11
影响因子：
5.3
通讯作者：
Szaro, Ben G.
中科院分区：
文献类型：
--
作者：
Hutchins, Erica J.;Szaro, Ben G.
c-Jun n -末端激酶（JNK）介导轴突生长所必需的细胞信号传导，但相关的底物和潜在的机制尚不清楚。我们在非洲爪蟾胚胎中发现了一种新的转录后机制，即JNK通过磷酸化异质核糖核蛋白K （hnRNP K）上的一个特定位点来调节轴突发生。JNK抑制和hnRNP K敲低都抑制了轴突的生长和hnRNP K调控的细胞骨架rna （tau和神经丝培养基）的翻译，这种影响通过表达拟磷而不是缺磷而得到缓解。免疫组织化学和生化分析表明，hnRNP K的JNK磷酸化发生在细胞质内，并且是hnRNP K靶向RNA翻译起始所必需的，但不是hnRNP K细胞内定位或RNA结合所必需的。因此，除了在转录和细胞骨架组织中已知的作用外，JNK还通过hnRNP K转录后调节轴突发生中至关重要的蛋白质的翻译。
c-Jun N-terminal kinase (JNK) mediates cell signaling essential for axon outgrowth, but the associated substrates and underlying mechanisms are poorly understood. We identified in Xenopus laevis embryos a novel posttranscriptional mechanism whereby JNK regulates axonogenesis by phosphorylating a specific site on heterogeneous nuclear ribonucleoprotein K (hnRNP K). Both JNK inhibition and hnRNP K knockdown inhibited axon outgrowth and translation of hnRNP K-regulated cytoskeletal RNAs (tau and neurofilament medium), effects that were alleviated by expressing phosphomimetic, but not phosphodeficient, forms of hnRNP K. Immunohistochemical and biochemical analyses indicated that JNK phosphorylation of hnRNP K occurred within the cytoplasm and was necessary for the translational initiation of hnRNP K-targeted RNAs but not for hnRNP K intracellular localization or RNA binding. Thus, in addition to its known roles in transcription and cytoskeletal organization, JNK acts posttranscriptionally through hnRNP K to regulate translation of proteins crucial for axonogenesis.