| Theme | New aspect of calcium, magnesium and phosphate transport -- Basic principles and clinical applications | |
|---|---|---|
| Title | Molecular functions of α-Klotho in calcium homeostasis | |
| Publish Date | 2007/01 | |
| Author | Youichi Nabeshima | Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University |
| [ Summary ] | α-klotho mutant mice have an average life span of about two months and display a variety of aging related phenotypes. Increased vitamin D activity, perhaps in combination with altered mineral homeostasis, causes almost all phenotypes observed in α-klotho-l- mice, because the lowering of vitamin D activity, either by dietary restriction or genetic ablation of 1α-hydroxylase in α-klotho-l- mice can significantly rescue the premature aging-like phenotypes and subsequently prolonged the survival in α-klotho mutant mice. α-Klotho plays crucial roles in the key steps of the regulatory network for calcium homeostasis, since α-Klotho is pivotal in the synthesis of 1, 25 (OH)2D3 the secretion of PTH and the rapid regulation of transepithelial calcium transportation in the choroid plexus and DCT nephrons in the kidneys. α-Klotho is essential for the recognition of FGF23 by target cells as well as Ca2+ mediated recruitment of Na+, K+-ATPase to the cell surface, both working as primary role in the complicated, but well organized regulation of calcium homeostasis. Furthermore, α-Klotho takes part in the regulation of calcium homeostasis of CSF in the choroid plexus, and of blood and bodily fluids in the parathyroid glands and DCT. In this regard, α-Klotho might play a pivotal role in the regulation of calcium metabolism as a central regulator of calcium homeostasis. |
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