PICK1 links Argonaute 2 to endosomes in neuronal dendrites and regulates miRNA activity.
PICK1 links Argonaute 2 to endosomes in neuronal dendrites and regulates miRNA activity.
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DOI：
10.1002/embr.201337631
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发表时间：
2014-05
期刊：
影响因子：
7.7
通讯作者：
Hanley, Jonathan G.
中科院分区：
文献类型：
--
作者：
Antoniou, Anna;Baptista, Marcio;Carney, Nicholas;Hanley, Jonathan G.
MicroRNAs通过抑制信使核糖核酸靶标的翻译来微调基因的表达。ArgAerte(AGO)蛋白是microRNA诱导转录后沉默的关键介质，已被证明与内体隔室有关，但这一过程的分子机制尚不清楚，特别是在神经元中。在这里，我们报道了Ago2和BAR结构域蛋白PICK1之间的一种新的相互作用。我们发现PICK1促进Ago2在神经元树突的内体隔室定位，并抑制Ago2在神经元刺激后的翻译抑制中的功能。我们认为，PICK1在依赖活性的内体转运和神经元翻译的局部调控之间提供了联系。
MicroRNAs fine-tune gene expression by inhibiting the translation of mRNA targets. Argonaute (Ago) proteins are critical mediators of microRNA-induced post-transcriptional silencing and have been shown to associate with endosomal compartments, but the molecular mechanisms that underlie this process are unclear, especially in neurons. Here, we report a novel interaction between Ago2 and the BAR-domain protein, PICK1. We show that PICK1 promotes Ago2 localization at endosomal compartments in neuronal dendrites and inhibits Ago2 function in translational repression following neuronal stimulation. We propose that PICK1 provides a link between activity-dependent endosomal trafficking and local regulation of translation in neurons.
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