Journal Article

The β-glucuronidase klotho exclusively activates the epithelial Ca<sup>2+</sup> channels TRPV5 and TRPV6

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

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 23, issue 11, pages 3397-3402
Published in print November 2008 | ISSN: 0931-0509
Published online May 2008 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfn291
The β-glucuronidase klotho exclusively activates the epithelial Ca2+ channels TRPV5 and TRPV6

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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

Journal Article.  3353 words.  Illustrated.

Subjects: Nephrology

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