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Nephrol Dial Transplant. 2008 Nov;23(11):3397-402. doi: 10.1093/ndt/gfn291. Epub 2008 May 21.

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

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  • 1Department of Physiology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

Abstract

BACKGROUND:

Active Ca(2+) reabsorption in the kidney is facilitated by the epithelial transient receptor potential vanilloid Ca(2+) 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, beta-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 beta-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 Ca(2+)-influx measurements.

RESULTS:

Klotho and beta-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 Ca(2+) channels TRPV5 and TRPV6.

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