The translation repressor 4E-BP2 is critical for eIF4F complex formation, synaptic plasticity, and memory in the hippocampus
The translation repressor 4E-BP2 is critical for eIF4F complex formation, synaptic plasticity, and memory in the hippocampus
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DOI：
10.1523/jneurosci.2423-05.2005
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发表时间：
2005-10-19
影响因子：
5.3
通讯作者：
Klann, E
中科院分区：
文献类型：
--
作者：
Banko, JL;Poulin, F;Klann, E
持久的突触可塑性和记忆需要信使核糖核酸（mRNA）的翻译，但人们对这一过程是如何被调控的知之甚少。为了探究翻译抑制因子4E - BP2在海马长时程增强（LTP）以及学习和记忆中所起的作用，我们对4E - BP2基因敲除小鼠进行了研究。有趣的是，4E - BP2的基因缺失使谢弗侧支通路中的早期LTP转变为晚期LTP（L - LTP），这可能是由于真核起始因子4F（eIF4F）复合物形成增加以及翻译起始增强所致。在4E - BP2基因敲除小鼠中，揭示了活动诱导翻译的一个关键限制，因为传统刺激模式所引发的L - LTP受到了阻碍。此外，4E - BP2基因敲除小鼠还表现出空间学习和记忆受损以及条件性恐惧关联记忆缺陷。这些结果表明，在小鼠海马的LTP以及学习和记忆过程中，4E - BP2对eIF4F复合物的适当调控起着至关重要的作用。
Long-lasting synaptic plasticity and memory requires mRNA translation, yet little is known as to how this process is regulated. To explore the role that the translation repressor 4E-BP2 plays in hippocampal long-term potentiation (LTP) and learning and memory, we examined 4E-BP2 knock-out mice. Interestingly, genetic elimination of 4E-BP2 converted early-phase LTP to late-phase LTP (L-LTP) in the Schaffer collateral pathway, likely as a result of increased eIF4F complex formation and translation initiation. A critical limit for activity-induced translation was revealed in the 4E-BP2 knock-out mice because L-LTP elicited by traditional stimulation paradigms was obstructed. Moreover, the 4E-BP2 knock-out mice also exhibited impaired spatial learning and memory and conditioned fear-associative memory deficits. These results suggest a crucial role for proper regulation of the eIF4F complex by 4E-BP2 during LTP and learning and memory in the mouse hippocampus.