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Klotho: a novel regulator of calcium and phosphorus homeostasis

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Abstract

Klotho which was originally identified as an anti-aging protein is emerging as a substance with multiple effects on many systems including mineral homeostasis. In addition to its membrane-bound function as a co-receptor for fibroblast growth factor-23, soluble Klotho exerts effects as a circulating substance in plasma and urine. Novel features of this system include its autocrine–paracrine–endocrine glycan-modifying enzymatic function in the urinary lumen on calcium and phosphate transporters. Klotho induces phosphaturia by inhibiting the proximal tubule Na-coupled phosphate transporter. The action of Klotho is enzymatic in nature which includes alteration of transport activity and the more traditional means of regulation by trafficking. Klotho reduces calciuria by its distal as a sialidase directly on the apical calcium channel. Desialidation of the channel exposes glycan residues that promote binding to galectin-1, resulting in stabilization of residence on the plasma membrane. Through its systematic as well as renal actions, Klotho is emerging as a principal calciophosphoregulatory hormone.

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Acknowledgments

The authors are supported by the Simmons Family Foundation, the National Institutes of Health (DK081523, AI041612, DK081423, HL096862, DK078708, DK 078596), the O’Brien Center of Kidney Research (DK-079328), and the Charles and Jane Pak Center of Mineral Metabolism.

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  1. Department of Internal Medicine, Charles and Jane Pak Center of Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX, 75390–8856, USA

    Chou-Long Huang & Orson W. Moe

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Huang, CL., Moe, O.W. Klotho: a novel regulator of calcium and phosphorus homeostasis. Pflugers Arch - Eur J Physiol 462, 185–193 (2011). https://doi.org/10.1007/s00424-011-0950-5

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