α-Klotho as a Regulator of Calcium Homeostasis

Akihiro Imura,Yoshihito Tsuji,Miyahiko Murata,Ryota Maeda, Koji Koyama,Akiko Iwano,Chikashi Obuse, Katsumi Togashi,Makoto Tominaga,Naoko Kita, Katsunori Tomiyama, Junko Iijima,Yoko Nabeshima, Makio Fujioka,Ryo Asato,Shinzo Tanaka,Ken Kojima,Juichi Ito,Kazuhiko Nozaki,Nobuo Hashimoto,Tetsufumi Ito,Takeshi Nishio,Takashi Uchiyama,Toshihiko Fujimori,Yo‐ichi Nabeshima

Science（2007）

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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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Key words

calcium homeostasis

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