Discovery of alpha-Klotho unveiled new insights into calcium and phosphate homeostasis.
alpha-Klotho was first identified as the responsible gene in a mutant mouse line whose disruption results in a variety of premature aging-related phenotypes. alpha-Klotho has been shown to participate in the regulation of parathyroid hormone secretion and trans-epithelial transport of Ca(2+) in the choroid plexus and kidney. alpha-Klotho, acting as a cofactor for FGF23, is also a major regulator of vitamin D biosynthesis and phosphate reabsorption in the kidney. These suggest that alpha-Klotho is a key player that integrates a multi-step regulatory system of calcium and phosphate homeostasis. Collectively, the molecular function of alpha-Klotho reveals a new paradigm that may change current concepts in mineral homeostasis and give rise to new insights in this field.
Nabeshima
Yo-ichi
Y
Department of Pathology and Tumor Biology, Kyoto University Graduate School of Medicine, Kyoto, Japan. nabemr@lmls.med.kyoto-u.ac.jp
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D000090265:Klotho Proteins; D010281:Parathyroid Hormone / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
C000717427:FGF23 protein, human; C000717428:Fgf23 protein, mouse; D010281:Parathyroid Hormone; D010710:Phosphates; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium