-Klotho as a Regulator of Calcium Homeostasis
Akihiro Imura,1,2,8*
Yoshihito Tsuji,1,5*
Miyahiko Murata,1,3*
Ryota Maeda,1,2
Koji Kubota,1,2
Akiko Iwano,1,8
Chikashi Obuse,9
Kazuya Togashi,10
Makoto Tominaga,10
Naoko Kita,1
Ken-ichi Tomiyama,1
Junko Iijima,1
Yoko Nabeshima,1
Makio Fujioka,7
Ryo Asato,4
Shinzo Tanaka,4
Ken Kojima,4
Juichi Ito,4
Kazuhiko Nozaki,5
Nobuo Hashimoto,5
Tetsufumi Ito,11
Takeshi Nishio,3
Takashi Uchiyama,6
Toshihiko Fujimori,1,8
Yo-ichi Nabeshima1,8
Abstract:
-klotho was identified as a gene associated with premature aging–like phenotypes characterized by short lifespan. In mice, we found the molecular association of -Klotho (-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 -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 -Kl in the regulation of calcium metabolism.
1 Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
2 Horizontal Medical Research Organization, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
3 Integrative Brain Science, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
4 Department of Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
5 Department of Neurosurgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
6 Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
7 Electron Microscopy Center, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
8 Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Saitama 332-0012, Japan.
9 Laboratory of Functional Networks for Chromosome Inheritance, Graduate School of Life Science, Hokkaido University, Sapporo 001-0021, Japan.
10 Section of Cell Signaling, Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, Aichi 444-8787, Japan.
11 Department of Anatomy, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan.
* These authors contributed equally to this work.
To whom correspondence should be addressed. E-mail: nabemr{at}lmls.med.kyoto-u.ac.jp
