| Project/Area Number |
16590192
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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 |
General pharmacology
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| Research Institution | Kobe Gakuin University (2005-2006)
Kobe University (2004) |
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Principal Investigator |
SHUNTOH Hisato Kobe Gakuin University, The Faculty of Rehabilitation, Professor, 総合リハビリテーション学部, 教授 (70206259)
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| Co-Investigator(Kenkyū-buntansha) |
KUNO Takayoshi Kobe University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (50144564)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2006: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2005: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2004: ¥800,000 (Direct Cost: ¥800,000)
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| Keywords | calcineurin / immunosuppressants / tacrolimus / membrane traffic / adaptin / small GTPase / 細胞内輸送 / Ryh1 / Ypt3 / ゴルジ / エンドソーム / PI4P5K / グルカン合成酵素阻害薬 / ホスフォリパーゼC / プロテインキナーゼC / Rho / Ca^<2+> / Mn^<2+>-ATPase / Mn^<2+>ホメオスタシス / ゴルジ体 / エンドゾーム / ENTHドメイン / エンドサイトーシス |
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| Research Abstract |
Calcineurin, a Ca^<2+>-and calmodulin-dependent protein phosphatase is a molecular target for the specific immunosuppressive drugs, such as cyclosporin A or tacrolimus. Calcineurin is enriched in the neural tissues, and also distributes broadly in other tissues. The structure of calcineurin is highly conserved from yeast to man.
We are studying calcineurin signal transduction pathway in the fission yeast Schizosaccharomyces pombe (S. pombe) because this system is amenable to genetics and has many advantages in terms of relevance to higher systems. To identify gene products sharing an essential function with calcineurin, we have screened for mutations that confer synthetic lethality with calcineurin deletion. We have identified several complementation groups that may mediate the adverse effects of tacrolimus.
The combined use of powerful genetics and of specific calcineurin inhibitors in fission yeast identified new components of the calcineurin pathway, and defined new roles of calcineurin in the regulation of the many cellular processes. Recent our data have revealed functional interactions between calcineurin and adaptin μ subunit, Apm1 in the Golgi/endosome. Calcineurin also participates in membrane traffic through its functional connection with the small GTPases Ypt3 and Ryh1 in the Golgi/endosome.
These findings provide further insight into the mechanism underlying the adverse effect of tacrolimus.
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