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.
Lu, P., Boros, S., Chang, Q., Bindels, R. J., Hoenderop, J. G.,
["Department of Physiology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands."]
["Department of Physiology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands."]
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.
PMID: 18495742
 Screening
Validation: In vitro validation
Validation: In vivo validation
Characterization
Functional consequence
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Functional consequence
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| TRP channel | Interactor | Method | Post-translational modification | Subcellular trafficking | Activity | Reference | ||||||
| TRPV5 |
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Klotho | Calcium measurement | Activation | 18495742 | |||||||
| TRPV6 |
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Klotho | Calcium measurement | Activation | 18495742 | |||||||
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:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)