Department of Pharmacology, Perelman School of Medicine, Philadelphia, PA 19104-6084, USA.
Cell Rep. 2013 Oct 17;5(1):114-25. doi: 10.1016/j.celrep.2013.08.029. Epub 2013 Sep 26.
Protein synthesis in neuronal dendrites underlies long-term memory formation in the brain. Local translation of reporter mRNAs has demonstrated translation in dendrites at focal points called translational hotspots. Various reports have shown that hundreds to thousands of mRNAs are localized to dendrites, yet the dynamics of translation of multiple dendritic mRNAs has remained elusive. Here, we show that the protein translational activities of two dendritically localized mRNAs are spatiotemporally complex but constrained by the translational hotspots in which they are colocalized. Cotransfection of glutamate receptor 2 (GluR2) and GluR4 mRNAs (engineered to encode different fluorescent proteins) into rat hippocampal neurons demonstrates a heterogeneous distribution of translational hotspots for the two mRNAs along dendrites. Stimulation with s-3,5-dihydroxy-phenylglycine modifies the translational dynamics of both of these RNAs in a complex saturable manner. These results suggest that the translational hotspot is a primary structural regulator of the simultaneous yet differential translation of multiple mRNAs in the neuronal dendrite.
神经元树突中的蛋白质合成是大脑中长期记忆形成的基础。报告 mRNA 的局部翻译已经证明了在称为翻译热点的焦点处的树突中的翻译。各种报告表明，数百到数千个 mRNA 定位于树突中，但多个树突 mRNA 的翻译动力学仍然难以捉摸。在这里，我们表明，两种定位于树突中的 mRNA 的蛋白质翻译活性具有时空复杂性，但受到它们共定位的翻译热点的限制。将谷氨酸受体 2 (GluR2) 和谷氨酸受体 4 (GluR4) mRNA（工程改造以编码不同的荧光蛋白）共转染到大鼠海马神经元中，证明了这两种 mRNA 在树突中翻译热点的异质性分布。用 s-3,5-二羟基苯甘氨酸刺激以复杂的饱和方式改变了这两种 RNA 的翻译动力学。这些结果表明，翻译热点是神经元树突中多个 mRNA 同时但有差异翻译的主要结构调节剂。
