| Project/Area Number |
14380373
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neuroscience in general
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| Research Institution | RIKEN |
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Principal Investigator |
ENDO Shogo RIKEN, Research Unit, Unit Leader, 遠藤研究ユニット, ユニットリーダー (60192514)
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| Co-Investigator(Kenkyū-buntansha) |
TAKISHIMA Kunio National Defense Medical College, Professor, 生化学第一講座, 教授
IKEDA Toshio RIKEN, Lab.for Behavioral Genetics, Staff Scientist, 行動遺伝学技術開発チーム, 専門職研究員 (80252526)
LAUNEY Thomas RIKEN, Lab.for Memory and Learning, Staff Scientist, 記憶学習機構研究チーム, 研究員 (30322704)
SATOH Yasushi National Defense Medical College, Assistant Professor, 生化学第一講座, 助手
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥14,800,000 (Direct Cost: ¥14,800,000)
Fiscal Year 2004: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2003: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 2002: ¥6,400,000 (Direct Cost: ¥6,400,000)
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| Keywords | MAP kinase / nuclear translocation / gene deficient mice / Cre-LoxP / ERK2 / loxP / Cre / IoxP |
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| Research Abstract |
MAPK family proteins play essential roles in a variety of physiological phenomena including cell division, cell differentiation and growth. However, the roles of MAPK in non-dividing cell are relatively unknown compared to those of dividing cells. We chose the neuronal cells as a model to examine the role of ERK1/2, prototype members of MAPK family.
ERK2 protein plays an essential role in LTP in hippocampus and also in cerebellar. In addition, it plays a major role in memory of Aplysia. In this research project, we have proved the close association of the NO pathway and ERK pathway in cerebellar LTD. Further, we showed that ERKs may be involved in LTD through the declustering of AMPA-type glutamate receptors in cerebellar Purkinje cells.
The role of ERKs thought to be not only the phosphorylation of cytosolic proteins upon the activation but also the regulation of transcription after activated ERKs translocated into the cell nuclear. ERKs are assumed to be essential in cerebellar LTD and
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cerebellar-dependent memory. We have generated the mice lacking Erk2 gene specifically in Purkinje cells using Cre-loxP system. We proved that the mice lack ERK2 protein only in Purkinje cells. We are currently analyzing a variety of behaviors for the mice especially on the cerebellar-dependent memory such as eye-blink conditioning. Hopefully, this conditional knockout technique will provide the clue for cerebellar-dependent long-term memory, which cannot be examined using null knockout technique because ERK2 null knockout mice are embryonically lethal.
We established the system that enabled us to observe the activation of ERK2 and the translocation of ERK2 simultaneously. Using this system, we have found that dimerization of ERK2 plays an essential role in its translocation into the cell nuclear. Further we also showed that the efficient translocation of ERK2 required not only MEK-ERK pathway but the contribution from other kinase pathway. On the course of research, we have developed a variety of ERK2 mutants which have a variety of deficiency in their cellular translocation. These mutant ERK2 may work as good tool to probe the physiological function of ERK2 in future. Less
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