alpha-Klotho as a regulator of calcium homeostasis |
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| Authors: | Imura Akihiro Tsuji Yoshihito Murata Miyahiko Maeda Ryota Kubota Koji Iwano Akiko Obuse Chikashi Togashi Kazuya Tominaga Makoto Kita Naoko Tomiyama Ken-ichi Iijima Junko Nabeshima Yoko Fujioka Makio Asato Ryo Tanaka Shinzo Kojima Ken Ito Juichi Nozaki Kazuhiko Hashimoto Nobuo Ito Tetsufumi Nishio Takeshi Uchiyama Takashi Fujimori Toshihiko Nabeshima Yo-ichi |
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| Affiliation: | Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan. |
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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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