2003 Fiscal Year Final Research Report Summary
Identification of novel genes closely related to Alzheimer's disease
| Project/Area Number |
14580722
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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 |
Nerve anatomy/Neuropathology
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| Research Institution | RIKEN (The Institute of Physical and Chemical Research) |
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Principal Investigator |
OYAMA Fumitaka RIKEN (The Institute of Physical and Chemical Research), Brain Science Institute, Laboratory for Structural Neuropathology, Research Scientist, 構造神経病理研究チーム, 研究員 (40194641)
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| Project Period (FY) |
2002 – 2003
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| Keywords | Alzheimer's disease / tau / tau deficient mouse / transcriptome / Gem GTPase / cell elongation activity |
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| Research Abstract |
Tau, one of the major microtubule-associated proteins, is involved in neuronal cell morphogenesis and axonal maintenance. Tau is also the major component of paired helical filaments found in the brain affected by Alzheimer's disease. To explore an as yet unidentified role of tau in vivo, 〜11,000 mRNAs were profiled from tau-deficient mouse brains, and compared with those from control brains at the same age. The expression of Gem GTPase, a small GTP binding protein of the ras superfamily, was significantly increased in the brain of tau-deficient mice at eight weeks of age. Because Gem GTPase is a negative regulator of the Rho-Rho kinase pathway for cytoskeletal regulation, this protein was transiently overexpressed in CHO cells that do not express tau. Overexpression of Gem GTPase induced a marked elongation of CHO cells, and simultaneous expression of tau eliminated this effect, although tau is not bound directly to Gem GTPase. This anti-elongation activity of tau was attributed to its microtubule (MT)-binding domain, and homologous domains of MAP2 and MAP4 exhibit similar antagonistic activities. Taken together, the present results indicate that the level of Gem GTPase and its cell elongation activity are modulated by tau, and suggest that tau may be involved in a Gem GTPase-mediated signal transduction pathway.
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Research Products
(2 results)
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[Publications] Oyama, F., Kotliarova, S., Harada, A., Ito, M., Miyazaki, H., Ueyama, Y., Hirokawa, N., Nukina, N., Yasuo Ihara: "Gem GTPase and tau : morphological changes induced by Gem GTPase in CHO cells are antagonized by tau."J.Biol.Chem.. (In press). (2004)
Description
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