alpha-Klotho as a regulator of calcium homeostasis.
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.
Imura
Akihiro
A
Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
Tsuji
Yoshihito
Y
Murata
Miyahiko
M
Maeda
Ryota
R
Kubota
Koji
K
Iwano
Akiko
A
Obuse
Chikashi
C
Togashi
Kazuya
K
Tominaga
Makoto
M
Kita
Naoko
N
Tomiyama
Ken-ichi
K
Iijima
Junko
J
Nabeshima
Yoko
Y
Fujioka
Makio
M
Asato
Ryo
R
Tanaka
Shinzo
S
Kojima
Ken
K
Ito
Juichi
J
Nozaki
Kazuhiko
K
Hashimoto
Nobuo
N
Ito
Tetsufumi
T
Nishio
Takeshi
T
Uchiyama
Takashi
T
Fujimori
Toshihiko
T
Nabeshima
Yo-ichi
Y
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
D004791:Enzyme Inhibitors; D010281:Parathyroid Hormone; D010042:Ouabain; D005966:Glucuronidase; D000090265:Klotho Proteins; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium