Analyses of the glycan structure of which Klotho recognizes

Klotho 识别的聚糖结构分析

• 批准号: 21390058
• 负责人: IMURA Akihiko
• 金额: $ 11.32万
• 依托单位: 公益財団法人先端医療振興財団 (2011)Kyoto University (2009-2010)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21390058/
• 关键词: 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

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.

Beta-Klotho是一种Ⅰ型单跨膜蛋白，具有两个串联的糖基化酶样结构域，主要在肝细胞中表达。基因β-Klotho和α-Klotho属于Klotho家族。FGF 19被鉴定为脂质介质;其控制胆汁酸合成以调节脂质摄入。FGF 19蛋白在回肠中表达以将信号输入肝脏。β-Klotho的表达是信号所必需的。与α-Klotho一样，β-Klotho也识别单糖。因此，我们推断单糖附着于FGF 19蛋白。我们使用一种针对独特聚糖的抗体，鉴定了β-Klotho识别的特异性聚糖。我们的研究揭示了这些Klotho凝集素如何转导FGF信号。此外，我们已经表明，α-Klotho通过相同的识别系统结合NaK-ATPase。与此同时，人们已经了解了一种蛋白质如何与不同的结合伙伴、成纤维细胞生长因子家族和NaK-ATP酶复合物结合。我们的理解将有助于解决尚未解决的问题，即生理蛋白质（例如NaK-ATP酶复合物）如何被招募到表面膜。也就是说，应当理解，通过几种糖基转移酶对糖基化的调节调节生理分子的转运。可以预见，对聚糖生物学意义的更广泛的研究将得到推广。

项目成果

αクロトーが認識する糖鎖の構造決定とシグナル様式の解明

α-Klotho 识别的糖链结构的测定和信号模式的阐明

• 发表时间: 2011
• 作者: Setiawan;N.;Osanai;Y.;Nakano;N.;Adachi;T.;Yonemura;K.;Yoshimoto;A.;伊村明浩
• 通讯作者: 伊村明浩

メタボリックFGFによる代謝の統合制御

代谢性 FGF 对代谢的综合控制

• 发表时间: 2011
• 期刊: 実験医学
• 作者: 鍋島陽一;伊村明浩;前田良太;Klotho
• 通讯作者: Klotho

Establishment of sandwich ELISA for soluble alpha-Klotho measurement: Age-dependent change of soluble alpha-Klotho levels in healthy subjects.

• DOI: 10.1016/j.bbrc.2010.06.110
• 发表时间: 2010-07-30
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Yamazaki, Yuji;Imura, Akihiro;Urakawa, Itaru;Shimada, Takashi;Murakami, Junko;Aono, Yukiko;Hasegawa, Hisashi;Yamashita, Takeyoshi;Nakatani, Kimihiko;Saito, Yoshihiko;Okamoto, Nozomi;Kurumatani, Norio;Namba, Noriyuki;Kitaoka, Taichi;Ozono, Keiichi;Sakai, Tomoyuki;Hataya, Hiroshi;Ichikawa, Shoji;Imel, Erik A.;Econs, Michael J.;Nabeshima, Yo-ichi
• 通讯作者: Nabeshima, Yo-ichi

クロトーは修飾糖鎖を認識することでFGFシグナルを伝える

Klotho 通过识别修饰糖链来传输 FGF 信号

• 发表时间: 2012
• 作者: 前田良太;伊村明浩
• 通讯作者: 伊村明浩

遠位尿細管、副甲状腺、脈絡膜に発現する体液カルシウムセンサーの解明

阐明远端肾小管、甲状旁腺和脉络膜中表达的体液钙传感器

• 发表时间: 2009
• 作者: 伊藤詔子監修;新田玲子編共著;Saga Y;高村ゆかり;伊村明浩
• 通讯作者: 伊村明浩