2009 Fiscal Year Final Research Report
Bio-response system regulated by Klotho・Na+/K+ ATPase complex
| Project/Area Number |
17109004
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (S)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Pathological medical chemistry
|
|---|
| Research Institution | Kyoto University |
|---|
Principal Investigator |
NABESHIMA Yo-ichi Kyoto University, 大学院・医学研究科, 教授 (60108024)
|
|---|
| Project Period (FY) |
2005 – 2009
|
| Keywords | Klotho / Na^+ / K^+-ATPase / FGF23 / カルシウム / ビタミンD / 恒常性 / 早期老化 |
|---|
| Research Abstract |
α-Klotho binds to Na^+, K^+-ATPase and is rapidly translocated from endosomal organella to the plasma membrane together with Na^+, K^+-ATPase in response to altered extracellular calcium concentration. Increased Na^+ gradient produced by elevated Na^+, K^+-ATPase activity drives PTH secretion and transepithelial transport of calcium. β-Klotho is essential for FGF15 signaling and functions as a key regulator of bile acid/cholesterol metabolism. Detailed analyses revealed a comprehensive regulatory scheme of mineral homeostasis involving the mutually regulated positive/negative feedback actions of α-Klotho, FGF23 and 1,25(OH)_2D and an analogous regulatory network composed of β-Klotho, FGF15/humanFGF19 and bile acids that regulate bile acid/cholesterol metabolism. We also suggested Klotho-independent FGF21 signaling pathway(s). α-Klotho functions as a glyco-recognition/binding protein . The demonstrated molecular functions of α-Klotho provide a new paradigm that may change current concept in mineral homeostasis.
|
-
[Journal Article] Relevant use of Klotho in FGF19 subfamily signaling system in vivo.2010
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.
-
Journal Title
Proc. Natl. Acad. Sci. USA 107
Pages: 1666-1671
Peer Reviewed
-
-
-
-
-
[Journal Article] Nabehsima Yα-Klotho as a regulator of Calcium homeostasis2007
Author(s)
Imura A., Tsuji Y, Murata M., Maeda R. Kubota K., Iwano A., Obuse C., Togashi K., Tominaga M., Kita N., Tomiyama K., Iijima J., Nabehsima Y., Fujioka M., Asato R., Tanaka S., Kojima K. Ito J., Nozaki K., Hashimoto N., Ito T., Nishio T., Uchiyama T., Fujimori T.
-
Journal Title
Science 316
Pages: 1615-1618
Peer Reviewed
-
-
-
-
[Journal Article] Correlation between hyperphosphatemia and type II Na/Pi cotransporter activity in klotho mice.2006
Author(s)
Segawa H, Yamanaka S, Ohno Y, Onitsuka A, Shiozawa K, Aranami F, Furutani J, Tomoe Y, Ito M, Kuwahata M, Tatsumi S, Imura A, Nabeshima Y, Miyamoto KI.
-
Journal Title
Am J Physiol Renal Physiol. 292(2)
Pages: F769-779
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
