2005 Fiscal Year Final Research Report Summary
Identification and functional analysis of Cdk5-mediated phosphorylation of the proteins that are related to brain formation and development
| Project/Area Number |
15500273
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | RIKEN |
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Principal Investigator |
OHSHIMA Toshio RIKEN, Laboratory for Developmental Neurobiology, Deputy Team Leader, 発生神経生物研究チーム, 副チームリーダー (20311334)
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| Project Period (FY) |
2003 – 2005
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| Keywords | phosphorylation / serine / threonine kinase / cyclin-dependent kinase / GSK3β / tubulin / Reelin / Dab1 / Alzheimer's disease |
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| Research Abstract |
Purpose and Method :
Cdk5 is a neuron-specific Ser/Thr protein kinase and Cdk5 KO mice exhibit defective brain development particularly in layer formation of cortical structures. Abnormalities of brain development in Cdk5 KO mice are caused by defects in the phosphorylations of brain development related-proteins. Using brains from Cdk5 KO mice, we conducted a screening to identify Cdk5 substrate(s). Functional analysis of newly identified substrate(s) is further performed. We also studied the functional significance of Cdk5-mediated phosphorylation of Dab1 which is a intracellular mediator of Reelin signaling.
Results :
Through the screening, we identified CRMP2 as a substrate of Cdk5. Under the collaboration with Dr.Goshima's group in Yokohama City University School of Medicine, we found Cdk5 phosphorylates CRMP2 at Ser522. This phosphorylation is required for Ser509 phosphorylation by GSK3β. This sequential phosphorylation by Cdk5 and GSK3β reduces the affinity between CRMP2 and tubulins. We also demonstrate that this sequential phosphorylation of CRMP2 is related to the production of 3F4 reactivity specifically in the brains from Alzheimer's patients. In another study, we showed that Cdk5 phosphorylates Dab1 at multiple sites in its C-terminal. Cdk5-mediated Ser/Thr phosphorylations of Dab1 inhibit tyrosine phosphorylation of Dab1 induced by Reelin. This result indicates a negative modulation of Reelin signaling by Cdk5.
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[Journal Article] Semaphorin-3A signaling is mediated via sequential Cdk5-GSK3β phosphorylation of CRMP2 : implication of common phosphorylating mechanism underlying axon guidance and Alzheimer's disease.2005
Author(s)
Uchida, Y., Ohshima, T., Sasaki, Y., Suzuki, H., Yanai, S., Yamashita, N., Nakamura, F., Takei, K., Ihara, Y., Mikoshiba, K., Kolattukudy, P., Honnorat, J., Goshima, Y.
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Journal Title
Genes to Cells 10
Pages: 165-179
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Impairment of hippocampal long-term depression and defective spatial learning and memory in p35 mice.2005
Author(s)
Ohshima, T., Ogura, H., Tomizawa, K., Hayashi, K., Suzuki, H., Saito, T., Kamei, H., Nishi, A., Bibb, J.A., Hisanaga, S, Matsui, H., Mikoshiba, K.
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Journal Title
J Neurochem. 94
Pages: 917-925
Description
「研究成果報告書概要(欧文)」より
