Am J Physiol Renal Physiol. 2006 May;290(5):F1253-9. Epub 2005 Dec 13.

The immunophilin FKBP52 inhibits the activity of the epithelial Ca2+ channel TRPV5.External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c

Gkika, D., Topala, C. N., Hoenderop, J. G., Bindels, R. J.,
["286 Cell Physiology, Radboud Univ. Nijmegen Medical Centre, PO Box 9101, NL-6500 HB Nijmegen, The Netherlands."]
In the kidney, the epithelial Ca(2+) channel TRPV5 constitutes the apical entry pathway in the process of active Ca(2+) reabsorption. The regulation of Ca(2+) influx through TRPV5 is of crucial importance, because it determines the final amount of Ca(2+) excreted in the urine. The present study identifies FKBP52 as an auxiliary protein of TRPV5, inhibiting channel activity. FKBP52 shows specific interaction with TRPV5, and both proteins colocalize in the distal part of the nephron. On the functional level, FKBP52 decreases Ca(2+) influx through TRPV5 as demonstrated in radioactive (45)Ca(2+) uptake measurements and electrophysiological studies in TRPV5-overexpressing human embryonic kidney 293 cells. On the other hand, gene silencing of FKBP52 or administration of the FKBP52 blocker FK-506 enhances Ca(2+) influx through TRPV5. The inhibitory action of FKBP52 on TRPV5 activity is blunted by mutation of its peptidyl-propyl cis-trans isomerase domain, showing that the FKBP52 catalytic property is critical for channel activity. In conclusion, these results suggest that FKBP52 plays an important role in the regulation of TRPV5 and thus in the process of Ca(2+) reabsorption.
PMID: 16352746External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c
Screening Toggle 893349bafcc528f8346c51dc3420151d67b0126b2c122dd1017121c03fa0f69b
  Experimental screening Non-experimental screening Reference
TRP channel construct Interactor source
TRP channel Interactor Method Species Region Species Organ/tissue Sample type
TRPV5 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 FKBP52/FKBP4 Inference Prediction 16352746
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Validation: In vitro validation Toggle 893349bafcc528f8346c51dc3420151d67b0126b2c122dd1017121c03fa0f69b
  Assay with recombinant proteins Reference
TRP channel construct Interactor construct
TRP channel Interactor Method Species Region Expression system Species Region Expression system
TRPV5 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 FKBP52/FKBP4 Fusion protein-pull down assay Mouse Full-length In vitro translation Mouse Full-length E. coli 16352746
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Validation: In vivo validation Toggle 893349bafcc528f8346c51dc3420151d67b0126b2c122dd1017121c03fa0f69b
  Assay with endogenous proteins Assay with overexpressed proteins Reference
Cell or tissue Cell or tissue TRP channel construct Interactor construct
TRP channel Interactor Method Species Region Species Region
TRPV5 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 FKBP52/FKBP4 Co-immunoprecipitation HEK293 Mouse Full-length Not used 16352746
TRPV5 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 FKBP52/FKBP4 Co-immunofluorescence staining Mouse kidney section 16352746
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Functional consequence Toggle 893349bafcc528f8346c51dc3420151d67b0126b2c122dd1017121c03fa0f69b
TRP channel Interactor Method Post-translational modification Subcellular trafficking Activity Reference
TRPV5 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 FKBP52/FKBP4 Calcium measurement Inhibition 16352746
TRPV5 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 FKBP52/FKBP4 Patch clamp Inhibition 16352746
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
TRP / Interactor

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