HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 290/5/F1253    most recent 00298.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (8) Citing Articles via Google Scholar Google Scholar Articles by Gkika, D. Articles by Bindels, R. J. M. Search for Related Content PubMed PubMed Citation Articles by Gkika, D. Articles by Bindels, R. J. M.

The immunophilin FKBP52 inhibits the activity of the epithelial Ca²⁺ channel TRPV5

Department of Physiology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

Submitted 21 July 2005 ; accepted in final form 9 December 2005

In the kidney, the epithelial Ca²⁺ channel TRPV5 constitutes the apical entry pathway in the process of active Ca²⁺ reabsorption. The regulation of Ca²⁺ influx through TRPV5 is of crucial importance, because it determines the final amount of Ca²⁺ 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 Ca²⁺ influx through TRPV5 as demonstrated in radioactive ⁴⁵Ca²⁺ 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 Ca²⁺ 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 Ca²⁺ reabsorption.

ion channel; tacrolimus; FK506; ECaC; Ca²⁺ homeostasis

This article has been cited by other articles:

				J. P. H. Schoeber, S. F. J. van de Graaf, K. P. Lee, H. G. M. Wittgen, J. G. J. Hoenderop, and R. J. M. Bindels Conditional fast expression and function of multimeric TRPV5 channels using Shield-1 Am J Physiol Renal Physiol, January 1, 2009; 296(1): F204 - F211. [Abstract] [Full Text] [PDF]

				T. Stumpf, Q. Zhang, D. Hirnet, U. Lewandrowski, A. Sickmann, U. Wissenbach, J. Dorr, C. Lohr, J. W. Deitmer, and C. Fecher-Trost The Human TRPV6 Channel Protein Is Associated with Cyclophilin B in Human Placenta J. Biol. Chem., June 27, 2008; 283(26): 18086 - 18098. [Abstract] [Full Text] [PDF]