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NDT Advance Access published online on May 21, 2008
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfn291
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© The Author [2008]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org


The β-glucuronidase klotho exclusively activates the epithelial Ca2+ channels TRPV5 and TRPV6

Peng Lu, Sandor Boros, Qing Chang, René J. Bindels and Joost G. Hoenderop

Department of Physiology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

Correspondence and offprint requests to: Joost G. Hoenderop, 286 Physiology, PO Box 9101, 6500 HB Nijmegen, The Netherlands. Tel: +31-24-3610580; Fax: +31-24-3616413; E-mail: j.hoenderop{at}ncmls.ru.nl



  Abstract

Background. Active Ca2+ reabsorption in the kidney is facilitated by the epithelial transient receptor potential vanilloid Ca2+ channel subtype 5 (TRPV5). The complex-glycosylated TRPV5 is expressed at the apical membrane of the renal distal convoluted tubule (DCT) cells where the pro-urine hormone klotho can stimulate its activity by N-oligosaccharide hydrolysis. This study investigates whether klotho and its closely related analogue, β-glucuronidase, can activate other renal ion channels than TRPV5 expressed by DCT cells.

Methods. To determine the specificity of this stimulatory effect of klotho and β-glucuronidase, a selection of ion channels and transporters expressed in the kidney (TRPV4, TRPV5, TRPV6 and TRPM6) was screened in transfected HEK293 cells by using Ca2+-influx measurements.

Results. Klotho and β-glucuronidase have been found to significantly increase the activity of TRPV5 and TRPV6, but had no effect on TRPV4 and TRPM6. Furthermore, deglycosylation by endoglycosidase-F also stimulated the activity of TRPV4, TRPV5 and TRPV6, but not of TRPM6.

Conclusions. These results suggest a modulating effect for klotho primarily restricted to the epithelial Ca2+ channels TRPV5 and TRPV6.

Keywords: endoF; epithelial calcium channel; β-glucuronidase; klotho; N-glycosylation

Received for publication: 1.10.07
Accepted in revised form: 24. 4.08


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