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

Autor: René J. M. Bindels, Sandor Boros, Qing Chang, Peng Lu, Joost G. J. Hoenderop
Rok vydání: 2008
Předmět:
TRPV4
medicine.medical_specialty
TRPV5
TRPV Cation Channels
Membrane transport and intracellular motility [NCMLS 5]
030204 cardiovascular system & hematology
Transfection
urologic and male genital diseases
Cell Line
Metabolism
transport and motion [NCMLS 2]
03 medical and health sciences
Transient receptor potential channel
0302 clinical medicine
Internal medicine
medicine
Humans
Distal convoluted tubule
Kidney Tubules
Distal
Klotho Proteins
Klotho
Ion channel
Glucuronidase
Renal disorder [IGMD 9]
030304 developmental biology
0303 health sciences
Transplantation
Reabsorption
business.industry
Epithelial Cells
Apical membrane
Cell biology
Renal disorders [UMCN 5.4]
Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase
Endocrinology
medicine.anatomical_structure
Nephrology
Calcium
Calcium Channels
business
Zdroj: Nephrology, Dialysis, Transplantation, 23, 3397-402
Nephrology, Dialysis, Transplantation, 23, 11, pp. 3397-402
ISSN: 1460-2385
0931-0509
DOI: 10.1093/ndt/gfn291
Popis: Contains fulltext : 70822.pdf (Publisher’s version ) (Open Access) 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.
Databáze: OpenAIRE
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