The mRNA for elongation factor 1α is localized in dendrites and translated in response to treatments that induce long-term depression
The mRNA for elongation factor 1α is localized in dendrites and translated in response to treatments that induce long-term depression
复制标题
DOI：
10.1523/jneurosci.1779-05.2005
复制
发表时间：
2005-08-03
影响因子：
5.3
通讯作者：
Steward, O
中科院分区：
文献类型：
--
作者：
Huang, F;Chotiner, JK;Steward, O
越来越多的证据表明，活动依赖性突触可塑性的持久形式，如长期增强（LTP）和长期抑制（LTD），需要树突内局部合成蛋白质。鉴定新的树突mrna并确定它们的分布和翻译是如何调节的是一个高度优先事项。我们在这里证明了延伸因子1 α (EF1 α)的mRNA在体内存在于表现LTP和LTD的神经元树突中，并且其翻译受到局部调控。EF1 α mRNA的亚细胞分布不同于之前描述的任何树突状mRNA。在海马中，mRNA在细胞体中高表达，也集中于内分子层的交联/联合传入事件终止区，这表明mRNA的定位与不同类型突触的分布有一定的关系。然而，EF1 α mRNA的定位不会因为长时间的突触激活而改变，而长时间的突触激活足以引起Arc mRNA的剧烈重新分布。局部应用代谢性谷氨酸受体激动剂（R， S）-3,5-二羟基苯基甘氨酸（DHPG）导致树突中EF1 α蛋白的免疫染色急剧增加，并且用DHPG治疗海马切片导致EF1 α蛋白水平增加，DHPG已知会诱导LTD。这两种反应都被蛋白合成抑制剂大霉素阻断。相比之下，使用诱导LTP的刺激模式刺激穿通通路会导致活化树突层中EF1 α蛋白的免疫染色迅速增加，但这种增加不会被大霉素或雷帕霉素阻断。研究结果表明，EF1 α蛋白的局部合成可能对蛋白质合成依赖性LTD的突触机制很重要。
There is increasing evidence that long-lasting forms of activity-dependent synaptic plasticity, such as long-term potentiation ( LTP) and long-term depression ( LTD), require local synthesis of proteins within dendrites. Identifying novel dendritic mRNAs and determining how their distribution and translation is regulated is a high priority. We demonstrate here that the mRNA for the elongation factor 1 alpha ( EF1 alpha) is present in vivo in the dendrites of neurons that exhibit LTP and LTD, and that its translation is locally regulated. The subcellular distribution of EF1 alpha mRNA differs from any of the dendritic mRNAs that have been described previously. In the hippocampus, the mRNA is highly expressed in cell bodies and is also concentrated in the zone of termination of commissural/associational afferents in the inner molecular layer, suggesting that mRNA localization is in some way related to the distribution of different types of synapses. Nevertheless, the localization of EF1 alpha mRNA is not altered by prolonged periods of synaptic activation that are sufficient to cause a dramatic redistribution of Arc mRNA. Local application of the metabotropic glutamate receptor agonist ( R, S)-3,5-dihydroxyphenylglycine ( DHPG) led to dramatic increases in immunostaining for EF1 alpha protein in dendrites, and treatment of hippocampal slices with DHPG, which is known to induce LTD, led to increases in EF1 alpha protein levels. Both responses were blocked by the protein synthesis inhibitor anisomycin. In contrast, stimulation of the perforant path using patterns of stimulation that induce LTP caused rapid increases of immunostaining for EF1 alpha protein in the activated dendritic lamina, but these increases were not blocked by anisomycin or rapamycin. The findings suggest that local synthesis of EF1 alpha protein may be important for the synaptic mechanisms that underlie protein synthesis-dependent LTD.