α-Klotho as a Regulator of Calcium Homeostasis

Akihiro Imura(Kyoto University), Yoshihito Tsuji(Kyoto University), Miyahiko Murata(Kyoto University), Ryota Maeda(Kyoto University), Kôji Kubota(Kyoto University), Akiko Iwano(Kyoto University), Chikashi Obuse(Hokkaido University), Kazuya Togashi(National Institutes of Natural Sciences), Makoto Tominaga(National Institutes of Natural Sciences), Naoko Kita(Kyoto University), Kenichi Tomiyama(Kyoto University), Junko Iijima(Kyoto University), Yoko Nabeshima(Kyoto University), Yoko Nabeshima(Kyoto University), Makio Fujioka(Kyoto University), Ryo Asato(Kyoto University), Shinzo Tanaka(Kyoto University), Ken Kojima(Kyoto University), Juichi Ito(Kyoto University), Kazuhiko Nozaki(Kyoto University), Nobuo Hashimoto(Kyoto University), Tetsufumi Ito(Kyoto University), Takeshi Nishio(Kyoto University), Takashi Uchiyama(Kyoto University), Toshihiko Fujimori(Kyoto University), Yo‐ichi Nabeshima(Kyoto University), Yo‐ichi Nabeshima(Kyoto University)
Science
June 14, 2007
10.1126/science.1135901
Cited by 388

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.

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