Netrin-1 signaling regulates de novo protein synthesis of κ opioid receptor by facilitating polysomal partition of its mRNA
Netrin-1 signaling regulates de novo protein synthesis of κ opioid receptor by facilitating polysomal partition of its mRNA
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DOI：
10.1523/jneurosci.3014-06.2006
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发表时间：
2006-09-20
影响因子：
5.3
通讯作者：
Wei, Li-Na
中科院分区：
文献类型：
--
作者：
Tsai, Nien-Pei;Bi, Jing;Wei, Li-Na
κ阿片受体（KOR）的表达受到转录和转录后调控。我们报告说，KOR翻译的netrin-1调节的背根神经节（DRG）和P19胚胎癌细胞的初级神经元。在没有刺激的情况下，KOR mRNA的很大一部分保持在休眠状态，并在无活性的多核糖体后部分中分配。在netrin-1的刺激，激活其下游靶点粘着斑激酶（FAK），KOR mRNA迅速分区的抑制活性的多核糖体部分。在功能上，DRG神经元中新合成的KOR蛋白能够与特异性配体结合。本报告描述了netrin-1信号转导在药物受体KOR的翻译控制中的第一个例子，其中涉及netrin-1的介体FAK和一种新的机制，该机制增强了靶mRNA与多聚核糖体的结合以进行翻译激活。
The expression of kappa opioid receptor (KOR) is subjected to both transcriptional and posttranscriptional controls. We report that KOR translation is regulated by netrin-1 in primary neurons of dorsal root ganglion (DRG) and in P19 embryonal carcinoma cells. Without stimulation, a significant portion of KOR mRNA is maintained in a dormant state and partitions in the translationally inactive, post-polysomal fraction. During netrin-1 stimulation, which activates its downstream target focal adhesion kinase (FAK), KOR mRNA rapidly partitions to the translationally active polysomal fraction. Functionally, the newly synthesized KOR proteins in DRG neurons are able to bind to specific ligands. This report describes the first example of netrin-1 signaling in the translational control of a drug receptor KOR, which involves the mediator of netrin-1, FAK, and a novel mechanism that enhances the association of target mRNA with polysomes for translational activation.