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-klotho was identified as a gene associated with premature aging–likephenotypes characterized by short lifespan. In mice, we foundthe molecular association of -Klotho (-Kl) and Na+,K+-adenosinetriphosphatase (Na+,K+-ATPase) and provide evidence for an increaseof abundance of Na+,K+-ATPase at the plasma membrane. Low concentrationsof extracellular free calcium ([Ca2+]e) rapidly induce regulatedparathyroid hormone (PTH) secretion in an -Kl- and Na+,K+-ATPase–dependentmanner. The increased Na+ gradient created by Na+,K+-ATPaseactivity might drive the transepithelial transport of Ca2+ incooperation with ion channels and transporters in the choroidplexus and the kidney. Our findings reveal fundamental rolesof -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
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-Klotho as a Regulator of Calcium Homeostasis
-klotho was identified as a gene associated with premature aging–like phenotypes characterized by short lifespan. In mice, we found the molecular association of 
To whom correspondence should be addressed. E-mail: 
