| [ Summary ] |
α-Klotho was first identified as the gene responsible for insertion in mutant mouse line displaying a variety of aging-related phenotypes, particularly those caused by the abnormalities of mineral homeostasis. α-Klotho binds to Na+, K+-ATPase and regulates its activity by controlling Ca2+ dependent cell surface recruitment of Na+, K+-ATPase. Na+ gradients created by Na+, K+-ATPase activity derive the secretion of parathyroid hormone and trans-epithelial transport of Ca2+ in the choroid plexus and kidney.
α-Klotho, acting as a cofactor for FGF23 signaling, has also been shown to be a major regulator of vitamin D biosynthesis and phosphate reabsorption in the kidnies. These facts suggest that α-Klotho is a key player that integrates a multi-step regulatory system of calcium and phosphate homeostasis. Collectively, the demonstration of the molecular functions of α-Klotho provides a new paradigm that may change current concepts in mineral homeostasis and give rise to new insights in this field, although this concept requires further verification in the light of related findings. |