The immunophilin FKBP52 inhibits the activity of the epithelial Ca 2+ channel TRPV5
Résumé
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.