alpha-Klotho: a regulator that integrates calcium homeostasis.
Intensive study on calcium homeostasis regulation over the past several decades has established a systematized construal of its role in living phenomena, leaving us with the impression that this field is fairly defined and understood. However, the unveiling of the molecular function of alpha-Klotho has recently given new insight into this field. alpha-Klotho is a unique molecule that plays pivotal roles in: (i) the rapid tuning of extracellular Ca(2+) concentration through transepithelial Ca(2+) transport; (ii) parathyroid hormone secretion and subsequent Ca(2+) increase in the serum, and (iii) the signal transduction of FGF23 that adjusts the calcium concentration by downregulating the production of 1,25(OH)(2)D(3). Through these pathways, alpha-Klotho participates in the regulation of calcium homeostasis of the CSF and blood/body fluids by its actions in the choroid plexus, parathyroid glands and DCT nephrons. In this regard, alpha-Klotho is a key player that integrates 'a multi-step regulatory system of calcium homeostasis' that rapidly adjusts the extracellular calcium concentration and continuously maintains its concentration within a narrow physiological range.
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
Imura
Hiroaki
H
D019588:Aging, Premature / Q000378:metabolism; D000818:Animals; D002117:Calcitriol / Q000096:biosynthesis; D002118:Calcium / Q000378:metabolism*; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000378:metabolism; D005966:Glucuronidase / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology*; D000090265:Klotho Proteins; D008565:Membrane Proteins / Q000378:metabolism*; D010641:Phenotype; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D008565:Membrane Proteins; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins; D000254:Sodium-Potassium-Exchanging ATPase; D002117:Calcitriol; D002118:Calcium