2011 Fiscal Year Final Research Report
Analyses of the glycan structure of which Klotho recognizes
| 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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| Keywords | 受容体 / 細胞内シグナル伝達 |
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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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[Journal Article] Decreased renalα-Klotho expression in early diabetic nephropathy in humans and mice and its possible role in urinary calcium excretion2012
Author(s)
Asai O, Nakatani K, Tanaka T, Sakan H, Imura A, Yoshimoto S, Samejima K, Yamaguchi Y, Matsui M, Akai Y, Konishi N, Iwano M, Nabeshima Y, Saito Y
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Journal Title
Kidney Int
Volume: 81(6)
Pages: 539-47
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[Journal Article] Circulating levels of soluble alpha-Klotho are markedly elevated in human umbilical cord blood2011
Author(s)
Ohata Y, Arahori H, Namba N, Kitaoka T, Hirai H, Wada K, Nakayama M, Michigami T, Imura A, Nabeshima Y, Yamazaki Y, Ozono K
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Journal Title
J Clin Endocrinol Metab
Volume: 96(6)
Pages: E943-7
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[Journal Article] Establishment of sandwich ELISA for soluble alpha-Klotho measurement : Age-dependent change of soluble alpha-Klotho levels in healthy subjects2010
Author(s)
Yamazaki Y, Imura A, Urakawa I, Shimada T, Murakami J, Aono Y, Hasegawa H, Yamashita T, Nakatani K, Saito Y, Okamoto N, Kurumatani N, Namba N, Kitaoka T, Ozono K, Sakai T, Hataya H, Ichikawa S, Imel EA, Econs MJ, Nabeshima Y
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Journal Title
Biochem Biophys Res Commun
Volume: 398(3)
Pages: 513-8
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[Journal Article] Relevant use of Klotho in FGF19 subfamily signaling system in vivo2010
Author(s)
Tomiyama K, Maeda R, Urakawa I, Yamazaki Y, Tanaka T, Ito S, Nabeshima Y, Tomita T, Odori S, Hosoda K, Nakao K, Imura A, Nabeshima Y
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Journal Title
Proc Natl Acad Sci USA
Volume: 107(4)
Pages: 1666-71
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