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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*
Blood calcium concentration is maintained within a narrow rangedespite large variations in dietary input and body demand. TheTransient Receptor Potential ion channel TRPV5 has been implicatedin this process. We report here that TRPV5 is stimulated bythe mammalian hormone klotho. Klotho, a ß-glucuronidase,hydrolyzes extracellular sugar residues on TRPV5, entrappingthe channel in the plasma membrane. This maintains durable calciumchannel activity and membrane calcium permeability in kidney.Thus, klotho activates a cell surface channel by hydrolysisof 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}ncmls.ru.nl
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