Analyses of the glycan structure of which Klotho recognizes

β-Klotho是一种Ⅰ型单跨膜蛋白，具有两个串联的糖苷酶样结构域，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。同时，我们也了解了一种蛋白质是如何与FGF家族和NaK-ATP酶复合物结合的，这将有助于解决生理蛋白质如NaK-ATP酶复合物如何被募集到细胞膜表面的问题。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。

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.