title: alpha-Klotho as a regulator of calcium homeostasis.
abstract: alpha-klotho was identified as a gene associated with premature aging-like phenotypes characterized by short lifespan. In mice, we found the molecular association of alpha-Klotho (alpha-Kl) and Na+,K+-adenosine triphosphatase (Na+,K+-ATPase) and provide evidence for an increase of abundance of Na+,K+-ATPase at the plasma membrane. Low concentrations of extracellular free calcium ([Ca2+]e) rapidly induce regulated parathyroid hormone (PTH) secretion in an alpha-Kl- and Na+,K+-ATPase-dependent manner. The increased Na+ gradient created by Na+,K+-ATPase activity might drive the transepithelial transport of Ca2+ in cooperation with ion channels and transporters in the choroid plexus and the kidney. Our findings reveal fundamental roles of alpha-Kl in the regulation of calcium metabolism.
authors.affiliation: Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Imura
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Tsuji
authors.forename: Miyahiko
authors.initials: M
authors.lastname: Murata
authors.forename: Ryota
authors.initials: R
authors.lastname: Maeda
authors.forename: Koji
authors.initials: K
authors.lastname: Kubota
authors.forename: Akiko
authors.initials: A
authors.lastname: Iwano
authors.forename: Chikashi
authors.initials: C
authors.lastname: Obuse
authors.forename: Kazuya
authors.initials: K
authors.lastname: Togashi
authors.forename: Makoto
authors.initials: M
authors.lastname: Tominaga
authors.forename: Naoko
authors.initials: N
authors.lastname: Kita
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Tomiyama
authors.forename: Junko
authors.initials: J
authors.lastname: Iijima
authors.forename: Yoko
authors.initials: Y
authors.lastname: Nabeshima
authors.forename: Makio
authors.initials: M
authors.lastname: Fujioka
authors.forename: Ryo
authors.initials: R
authors.lastname: Asato
authors.forename: Shinzo
authors.initials: S
authors.lastname: Tanaka
authors.forename: Ken
authors.initials: K
authors.lastname: Kojima
authors.forename: Juichi
authors.initials: J
authors.lastname: Ito
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nozaki
authors.forename: Nobuo
authors.initials: N
authors.lastname: Hashimoto
authors.forename: Tetsufumi
authors.initials: T
authors.lastname: Ito
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nishio
authors.forename: Takashi
authors.initials: T
authors.lastname: Uchiyama
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Fujimori
authors.forename: Yo-ichi
authors.initials: Y
authors.lastname: Nabeshima
mesh_terms: D000818:Animals; D002118:Calcium / Q000134:cerebrospinal fluid / Q000378:metabolism*; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism; D002831:Choroid Plexus / Q000378:metabolism; D003593:Cytoplasm / Q000201:enzymology / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D025461:Feedback, Physiological; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006056:Golgi Apparatus / Q000378:metabolism; D006367:HeLa Cells; D006706:Homeostasis; D006801:Humans; D017136:Ion Transport; D007668:Kidney / Q000201:enzymology / Q000378:metabolism; D000090265:Klotho Proteins; D051379:Mice; D010042:Ouabain / Q000494:pharmacology; D010280:Parathyroid Glands / Q000201:enzymology / Q000378:metabolism; D010281:Parathyroid Hormone / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D010281:Parathyroid Hormone; D010042:Ouabain; D005966:Glucuronidase; D000090265:Klotho Proteins; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium