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Post-Training Dephosphorylation of eEF-2 Promotes Protein Synthesis for Memory Consolidation
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...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2757674/ https://www.ncbi.nlm.nih.gov/pubmed/19823585 http://dx.doi.org/10.1371/journal.pone.0007424 |
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author | Im, Heh-In Nakajima, Akira Gong, Bo Xiong, Xiaoli Mamiya, Takayoshi Gershon, Elliot S. Zhuo, Min Tang, Ya-Ping |
author_facet | Im, Heh-In Nakajima, Akira Gong, Bo Xiong, Xiaoli Mamiya, Takayoshi Gershon, Elliot S. Zhuo, Min Tang, Ya-Ping |
author_sort | Im, Heh-In |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-2757674 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-27576742009-10-13 Post-Training Dephosphorylation of eEF-2 Promotes Protein Synthesis for Memory Consolidation Im, Heh-In Nakajima, Akira Gong, Bo Xiong, Xiaoli Mamiya, Takayoshi Gershon, Elliot S. Zhuo, Min Tang, Ya-Ping PLoS One Research Article 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. Public Library of Science 2009-10-13 /pmc/articles/PMC2757674/ /pubmed/19823585 http://dx.doi.org/10.1371/journal.pone.0007424 Text en Im et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Im, Heh-In Nakajima, Akira Gong, Bo Xiong, Xiaoli Mamiya, Takayoshi Gershon, Elliot S. Zhuo, Min Tang, Ya-Ping Post-Training Dephosphorylation of eEF-2 Promotes Protein Synthesis for Memory Consolidation |
title | Post-Training Dephosphorylation of eEF-2 Promotes Protein Synthesis for Memory Consolidation |
title_full | Post-Training Dephosphorylation of eEF-2 Promotes Protein Synthesis for Memory Consolidation |
title_fullStr | Post-Training Dephosphorylation of eEF-2 Promotes Protein Synthesis for Memory Consolidation |
title_full_unstemmed | Post-Training Dephosphorylation of eEF-2 Promotes Protein Synthesis for Memory Consolidation |
title_short | Post-Training Dephosphorylation of eEF-2 Promotes Protein Synthesis for Memory Consolidation |
title_sort | post-training dephosphorylation of eef-2 promotes protein synthesis for memory consolidation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2757674/ https://www.ncbi.nlm.nih.gov/pubmed/19823585 http://dx.doi.org/10.1371/journal.pone.0007424 |
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