| Project/Area Number |
02454534
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
物質生物化学
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| Research Institution | The University of Tokyo |
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Principal Investigator |
NISHIDA Eisuke The University of Tokyo Faculty of Science Assistant Professor, 理学部, 助手 (60143369)
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| Co-Investigator(Kenkyū-buntansha) |
米沢 直人 東京大学, 理学部, 特別研究員(PD) (80212314)
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| Project Period (FY) |
1990 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1992: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1991: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1990: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | Actin-binding Proteins / Cytoskeleton / Phospholipase C / Inositol Phospholipid / Yeast / Dodecapeptide / アクチン結合蛋白質 / アクチン結合部位 / PIP_2 / ホスホリパ-ゼC / イノシト-ルリン脂質 / アクチン調節蛋白質 / 化学架橋 / 合成ペプチド |
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| Research Abstract |
Cofilin and destrin, low molecular weight actin-binding proteins, are related to each other. Cofilin depolymerizes F-actin in a pH- dependent manner, while destrin does in a pH-independent manner. We have found that the Trp^<104>-Met^<115> region of cofilin (and destrin) is an actin binding site, and that this region is a polyphosphoinositide-binding site. The synthetic dodecapeptide patterned on the sequence corresponding to this region binds to PIP2 (PIP) as well as actin tightly, and thus is a PIP2 (PIP)-sensitive inhibitor of actin polymerization. We have further found that cofilin and the dodecapeptide inhibit PIP2 hydrolysis catalyzed by phospholipase C. Therefore, cofilin may function not only as a regulator of actin cytoskeleton but also as a regulator of the phosphoinositide signaling pathway.
A cofilin-like protein has been identified from budding yeast. We carried out molecular cloning of this protein. We then expressed and purified a recombinant form of this protein, and characterized the recombinant protein. The results have shown that the protein depolymerizes F-actin in a pH-dependent manner, binds to both F- and G- actin, and binds to PIP2. These characteristics of the protein are completely the same as those of mammalian cofilin. Thus, we named this protein COF1. COF1 is found to be essential for yeast cell growth.
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