Facilitation of dendritic mRNA transport by CPEB
Facilitation of dendritic mRNA transport by CPEB
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DOI：
10.1101/gad.1053003
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发表时间：
2003-03-01
影响因子：
10.5
通讯作者：
Richter, JD
中科院分区：
文献类型：
--
作者：
Huang, YS;Carson, JH;Richter, JD
在神经元中，源自位于树突中的mRNA的蛋白质已经涉及突触可塑性。胞质多聚腺苷酸化元件（CPE）是特定树突状mRNA的T-UTR中的顺式元件，促进胞质多聚腺苷酸化诱导的翻译以响应突触刺激。在这里，我们证明了CPE及其结合蛋白CPEB促进mRNA运输到树突。在用重组病毒感染的大鼠海马神经元中，CPE足以指导报告RNA进入树突。CPEB-GFP蛋白形成含RNA的颗粒，其以微管依赖的方式以4-8 μ m/min的平均速度被运输到树突中。这样的颗粒还包含掩蔽蛋白（maskin），一种介导含CPE的mRNA的帽依赖性翻译抑制的CPEB相关因子，以及分子马达动力蛋白和驱动蛋白。CPEB在神经元中的过表达促进含有CPE的内源性MAP 2 mRNA向树突的运输，而与分子马达相互作用有缺陷的突变体CPEB的过表达抑制这种运输。在源自CPEB敲除小鼠的神经元中，含CPE的报告RNA的树突转运减少。这些结果表明一种机制，其中CPE-含有mRNA可以被运输到树突在一个休眠的形式，但在突触激活响应NMDA受体刺激。
In neurons, the proteins derived from mRNAs localized in dendrites have been implicated in synaptic plasticity. The cytoplasmic polyadenylation element (CPE), a cis element in the T-UTRs of specific dendritic mRNAs, promotes cytoplasmic polyadenylation-induced translation in response to synaptic stimulation. Here, we demonstrate that the CPE and its binding protein CPEB facilitate mRNA transport to dendrites. In rat hippocampal neurons infected with recombinant viruses, the CPE is sufficient to direct a reporter RNA into dendrites. CPEB-GFP protein forms RNA-containing particles that are transported into dendrites in a microtubule-dependent fashion at an average velocity of 4-8 mum/min. Such particles also contain maskin, a CPEB-associated factor that mediates cap-dependent translational repression of CPE-containing mRNA, and the molecular motors dynein and kinesin. Overexpression of CPEB in neurons promotes the transport of CPE-containing endogenous MAP2 mRNA to dendrites, whereas overexpression of a mutant CPEB that is defective for interaction with molecular motors inhibits this transport. in neurons derived from CPEB knockout mice, the dendritic transport of a CPE-containing reporter RNA is reduced. These results suggest a mechanism whereby CPE-containing mRNAs can be transported to dendrites in a translationally dormant form, but activated at synapses in response to NMDA receptor stimulation.