Journal
NEPHROLOGY DIALYSIS TRANSPLANTATION
Volume 23, Issue 11, Pages 3397-3402Publisher
OXFORD UNIV PRESS
DOI: 10.1093/ndt/gfn291
Keywords
endoF; epithelial calcium channel; beta-glucuronidase; klotho; N-glycosylation
Categories
Funding
- Netherlands Organization for Scientific Research [NWO-ALW 814.02.001, NWO-CW 700.55.302]
- European Science Foundation
- Dutch Kidney foundation [C06.2170, C03.6017]
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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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