| Project/Area Number |
21390058
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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 |
General physiology
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| Research Institution | 公益財団法人先端医療振興財団 (2011)
Kyoto University (2009-2010) |
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Principal Investigator |
IMURA Akihiko 公益財団法人先端医療振興財団, 先端医療センター, 主任研究員 (60362513)
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| Co-Investigator(Renkei-kenkyūsha) |
MAEDA Ryota 公益財団法人先端医療振興財団, 先端医療センター, 研究員 (50432399)
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| Project Period (FY) |
2010 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2011: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2010: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2009: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
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| Keywords | 受容体 / 細胞内シグナル伝達 / アルファークロトー / グルクロン酸 / 糖鎖 / レクチン / クロトーレクチンファミリー / 電解質(リン・カルシウム) / 表面プラズモン共鳴(SPR) / 線維芽細胞増殖因子(FGF) / 糖鎖有機合成 / 質量分析(MS-MS) / 原子間力顕微鏡(AFM) / 3-硫酸化グルクロン酸 |
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| Research Abstract |
Beta-Klotho, a type-I single-spanning membrane protein, has two tandem glycosidase-like domains and is expressed mainly in hepatocyte. The gene, beta-klotho, and alpha-Klotho belong to the Klotho family.
FGF19 was identified as a lipid mediator ; which controls bile acids synthesis to regulate lipid intake. The FGF19 protein is expressed in ileum to input signal in liver. Expression of the beta-Klotho is necessary for the signal.
Like alpha-Klotho, beta-Klotho recognizes a monosaccharide as well. Therefore, we deduced that the monosaccharide is attached to FGF19 protein. Using an antibody for unique glycan, we have identified the specific glycan of which beta-Klotho recognizes.
Our study revealed how these Klotho lectins transduces the FGF signals. Furthermore, we have shown that alpha-Klotho binds to NaK-ATPase through the same recognition system. Meanwhile, it has been understood how one protein can bind to distinct binding partners, FGF family and NaK-ATPase complex.
Our understandings will lead to solve unsolved questions that how physiological proteins, such as NaK-ATPase complex, are recruited to the surface membrane. That is, it would be understood that regulation of glycosylation by several glycosyl transferases regulates transports of the physiological molecules. It should be expected that more wide study to reveal biological significance of glycan would spread.
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