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. 2007 Jun 15;316(5831):1615-8.
doi: 10.1126/science.1135901.

alpha-Klotho as a regulator of calcium homeostasis

Akihiro Imura  1 , Yoshihito Tsuji, Miyahiko Murata, Ryota Maeda, Koji Kubota, Akiko Iwano, Chikashi Obuse, Kazuya Togashi, Makoto Tominaga, Naoko Kita, Ken-ichi 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
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alpha-Klotho as a regulator of calcium homeostasis

Akihiro Imura et al. Science. .

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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