Netrin-1信号通过促进κ阿片受体mRNA的多核糖体分配来调节其从头蛋白质合成。
Netrin-1 signaling regulates de novo protein synthesis of kappa opioid receptor by facilitating polysomal partition of its mRNA.
作者信息
Tsai Nien-Pei, Bi Jing, Loh Horace H, Wei Li-Na
机构信息
Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
出版信息
J Neurosci. 2006 Sep 20;26(38):9743-9. doi: 10.1523/JNEUROSCI.3014-06.2006.
Abstract
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.
摘要
κ-阿片受体（KOR）的表达受到转录和转录后调控。我们报告称，在背根神经节（DRG）的原代神经元和P19胚胎癌细胞中，KOR的翻译受netrin-1调控。在无刺激时，很大一部分KOR mRNA处于休眠状态，并分布于翻译无活性的多核糖体后组分中。在激活其下游靶点粘着斑激酶（FAK）的netrin-1刺激过程中，KOR mRNA迅速分布到翻译活性的多核糖体组分中。在功能上，DRG神经元中新合成的KOR蛋白能够与特定配体结合。本报告描述了netrin-1信号在药物受体KOR翻译调控中的首个实例，这涉及netrin-1的介质FAK以及一种增强靶mRNA与多核糖体结合以实现翻译激活的新机制。
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