NDT Advance Access originally published online on May 21, 2008
Nephrology Dialysis Transplantation 2008 23(11):3397-3402; doi:10.1093/ndt/gfn291
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The β-glucuronidase klotho exclusively activates the epithelial Ca2+ channels TRPV5 and TRPV6
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 |
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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
Received for publication: 1.10.07
Accepted in revised form: 24. 4.08
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