Post-training dephosphorylation of eEF-2 promotes protein synthesis for memory consolidation.
Post-training dephosphorylation of eEF-2 promotes protein synthesis for memory consolidation.
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DOI：
10.1371/journal.pone.0007424
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发表时间：
2009-10-13
期刊：
影响因子：
3.7
通讯作者：
Tang YP
中科院分区：
文献类型：
--
作者：
Im HI;Nakajima A;Gong B;Xiong X;Mamiya T;Gershon ES;Zhuo M;Tang YP
记忆巩固，将获得的信息转化为长期存储，是新的蛋白质合成依赖。由于蛋白质合成是一个受多种翻译机制控制的动态过程，然而，这些机制如何响应于记忆巩固的学习而被招募仍然是难以捉摸的。在这里，我们发现，真核延伸因子-2（eEF-2）显着去磷酸化在0.5-2小时内在海马和杏仁核的小鼠训练后的恐惧条件反射测试，而全基因组微阵列没有显示任何显着的变化的mRNA的表达水平的翻译机器或其相关分子。此外，在训练后立即用MK-801阻断NMDA受体显著阻碍了训练后eEF-2的去磷酸化和记忆保持。值得注意的是，通过一个优雅的复杂的转基因策略，我们证明了eEF-2激酶，一种特异性磷酸化并因此使eEF-2失活的激酶，在海马特异性过表达，显著抑制了海马中的蛋白质合成，并且这种作用在“正在进行的”蛋白质合成过程中更加稳健。结果，小鼠海马的晚期长时程增强（L-LTP）和长期海马依赖性记忆显著受损，而短期记忆和长期海马非依赖性记忆保持完整。这些结果揭示了一种新的翻译基础蛋白质合成有关的记忆巩固在哺乳动物大脑。
Memory consolidation, which converts acquired information into long-term storage, is new protein synthesis-dependent. As protein synthesis is a dynamic process that is under the control of multiple translational mechanisms, however, it is still elusive how these mechanisms are recruited in response to learning for memory consolidation. Here we found that eukaryotic elongation factor-2 (eEF-2) was dramatically dephosphorylated within 0.5–2 hr in the hippocampus and amygdala of mice following training in a fear-conditioning test, whereas genome-wide microarrays did not reveal any significant change in the expression level of the mRNAs for translational machineries or their related molecules. Moreover, blockade of NMDA receptors with MK-801 immediately following the training significantly impeded both the post-training eEF-2 dephosphorylation and memory retention. Notably, with an elegant sophisticated transgenic strategy, we demonstrated that hippocampus-specific overexpression of eEF-2 kinase, a kinase that specifically phosphorylates and hence inactivates eEF-2, significantly inhibited protein synthesis in the hippocampus, and this effects was more robust during an “ongoing” protein synthesis process. As a result, late phase long-term potentiation (L-LTP) in the hippocampus and long-term hippocampus-dependent memory in the mice were significantly impaired, whereas short-term memory and long-term hippocampus-independent memory remained intact. These results reveal a novel translational underpinning for protein synthesis pertinent to memory consolidation in the mammalian brain.
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影响因子：
5.3
作者：
Banko, JL;Poulin, F;Klann, E
通讯作者：
Klann, E
DOI：
10.1073/pnas.0505407103
发表时间：
2006-03-07
影响因子：
11.1
作者：
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通讯作者：
Tang, YP
影响因子：
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作者：
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通讯作者：
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影响因子：
64.8
作者：
Costa-Mattioli, M;Gobert, D;Sonenberg, N
通讯作者：
Sonenberg, N
影响因子：
64.5
作者：
BOURTCHULADZE, R;FRENGUELLI, B;SILVA, AJ
通讯作者：
SILVA, AJ