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Sci. Aging Knowl. Environ., 3 May 2006
Vol. 2006, Issue 8, p. pe11
[DOI: 10.1126/sageke.2006.8.pe11]

PERSPECTIVES

Toward a Better Understanding of Klotho

Yo-ichi Nabeshima

The author is in the Department of Pathology and Tumor Biology at Kyoto University Graduate School of Medicine, Yoshida Konoe-cho Sakyu-ku, Kyoto 606-8501, Japan. E-mail: nabemr{at}lmls.med.kyoto-u.ac.jp

http://sageke.sciencemag.org/cgi/content/full/2006/8/pe11

Key Words: Klotho • fibroblast growth factor 23 • premature aging • vitamin D • calcium homeostasis • phosphorus homeostasis • insulin/IGF-1 signaling

Abstract: klotho mutant mice were originally described as a short-lived mouse model with premature aging-like disorders. The klotho gene responsible for these phenotypes encodes a type I membrane protein with a considerable similarity to beta-glycosidase. klotho is predominantly expressed in tissues functioning in the regulation of calcium homeostasis. Suggested functions of Klotho are (i) a fundamental regulator of calcium homeostasis, namely, a cofactor for the fibroblast growth factor (FGF) receptor 1c in FGF23 signaling and a regulator of parathyroid hormone secretion; (ii) a hormone that interferes with the intracellular signaling of insulin and insulin-like growth factor-1; and (iii) a beta-glucuronidase that activates the transient receptor potential ion channel TRPV5 by trimming its sugar moiety. How can we reconcile these pleiotropic functions of Klotho? Is there any common mechanism? Further in vivo studies, and biochemical as well as physiological analyses, are required for a better understanding of the molecular aspects of Klotho.

Citation: Y.-i. Nabeshima, Toward a Better Understanding of Klotho. Sci. Aging Knowl. Environ. 2006 (8), pe11 (2006).

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