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Science 310 (5747): 490-493

Copyright © 2005 by the American Association for the Advancement of Science

The ß-Glucuronidase Klotho Hydrolyzes and Activates the TRPV5 Channel

Q. Chang, S. Hoefs, A. W. van der Kemp, C. N. Topala, R. J. Bindels, J. G. Hoenderop*

Abstract: Blood calcium concentration is maintained within a narrow range despite large variations in dietary input and body demand. The Transient Receptor Potential ion channel TRPV5 has been implicated in this process. We report here that TRPV5 is stimulated by the mammalian hormone klotho. Klotho, a ß-glucuronidase, hydrolyzes extracellular sugar residues on TRPV5, entrapping the channel in the plasma membrane. This maintains durable calcium channel activity and membrane calcium permeability in kidney. Thus, klotho activates a cell surface channel by hydrolysis of its extracellular N-linked oligosaccharides.

Department of Physiology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, Netherlands.

* To whom correspondence should be addressed. E-mail: J.Hoenderop{at}

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