| 7207836 | Concerted action of associated proteins in the regulation of TRPV5 and TRPV6. | Schoeber JP, etal., Biochem Soc Trans. 2007 Feb;35(Pt 1):115-9. | Ca(2+) is an essential ion in all organisms and many physiological functions in the body rely on the exact maintenance of the Ca(2+) balance. The epithelial Ca(2+) channels TRPV5 [TRP (transient receptor potential) vanilloid 5] and TRPV6 are the most Ca(2+)-sel ective members of the TRP superfamily and are generally considered as the gatekeepers of Ca(2+) entry across epithelia. TRPV5 is involved in Ca(2+) reabsorption from pro-urine, while TRPV6 has an essential role in intestinal Ca(2+) uptake. These channels are the prime targets of calciotropic hormonal regulation, including vitamin D and parathyroid hormone. In addition, extra- and intra-cellular signalling by associated proteins and Ca(2+) itself play key roles in TRPV5 and TRPV6 regulation. In this paper, we describe the present understanding of the concerted action of calbindin-D(28k), klotho and BSPRY (B-box and SPRY-domain-containing protein) at different levels throughout the epithelial cell to control Ca(2+) influx at the luminal entry gate. | 17233615 | 2007-02-01 |
| 7205490 | Rapid effects of 17beta-estradiol on TRPV5 epithelial Ca2+ channels in rat renal cells. | Irnaten M, etal., Steroids. 2009 Aug;74(8):642-9. doi: 10.1016/j.steroids.2009.02.002. Epub 2009 Feb 21. | The renal distal tubules and collecting ducts play a key role in the control of electrolyte and fluid homeostasis. The discovery of highly calcium selective channels, Transient Receptor Potential Vanilloid 5 (TRPV5) of the TRP superfamily, has clarified the natu re of the calcium entry channels. It has been proposed that this channel mediates the critical Ca(2+) entry step in transcellular Ca(2+) re-absorption in the kidney. The regulation of transmembrane Ca(2+) flux through TRPV5 is of particular importance for whole body calcium homeostasis.In this study, we provide evidence that the TRPV5 channel is present in rat cortical collecting duct (RCCD(2)) cells at mRNA and protein levels. We demonstrate that 17beta-estradiol (E(2)) is involved in the regulation of Ca(2+) influx in these cells via the epithelial Ca(2+) channels TRPV5. By combining whole-cell patch-clamp and Ca(2+)-imaging techniques, we have characterized the electrophysiological properties of the TRPV5 channel and showed that treatment with 20-50nM E(2) rapidly (<5min) induced a transient increase in inward whole-cell currents and intracellular Ca(2+) via TRPV5 channels. This rise was significantly prevented when cells were pre-treated with ruthenium red and completely abolished in cells treated with siRNA specifically targeting TRPV5.These data demonstrate for the first time, a novel rapid modulation of endogenously expressed TRPV5 channels by E(2) in kidney cells. Furthermore, the results suggest calcitropic effects of E(2). The results are discussed in relation to present concepts of non-genomic actions of E(2) in Ca(2+) homeostasis. | 19463684 | 2009-01-01 |
| 11521608 | Molecular Modeling of the Structural and Dynamical Changes in Calcium Channel TRPV5 Induced by the African-Specific A563T Variation. | Wang L, etal., Biochemistry. 2016 Mar 1;55(8):1254-64. doi: 10.1021/acs.biochem.5b00732. Epub 2016 Feb 15. | Transient receptor potential cation channels, vanilloid subfamily, member 5 (TRPV5) plays a key role in active Ca(2+) reabsorption in the kidney. Variations in TRPV5 occur at high frequency in African populations and may co ntribute to their higher efficiency of Ca(2+) reabsorption. One of the African specific variations, A563T, exhibits increased Ca(2+) transport ability. However, it is unclear how this variation influences the channel pore. On the basis of the structure of TRPV1, a TRPV5 model was generated to simulate the structural and dynamical changes induced by the A563T variation. On the basis of this model, amino acid residue 563 interacts with V540, which is one residue away from the key residue, D542, involved in Ca(2+) selectivity and Mg(2+) blockade. The A563T variation increases secondary structure stability and reduces dynamical motion of D542. In addition, the A563T variation alters the electrostatic potential of the outer surface of the pore. Differences in contact between selective filter residues and residue 563 and in electrostatic potential between the two TRPV5 variants were also observed in another model derived from an alternative alignment in the selective filters between TRPV5 and TRPV1. These findings indicate that the A563T variation induces structural, dynamical, and electrostatic changes in the TRPV5 pore, providing structural insight into the functional alterations associated with the A563T variation. | 26837804 | 2016-08-01 |
| 11536255 | WNK3 positively regulates epithelial calcium channels TRPV5 and TRPV6 via a kinase-dependent pathway. | Zhang W, etal., Am J Physiol Renal Physiol. 2008 Nov;295(5):F1472-84. doi: 10.1152/ajprenal.90229.2008. Epub 2008 Sep 3. | WNK3, a member of the With No Lysine (K) family of protein serine/threonine kinases, was shown to regulate members of the SLC12A family of cation-chloride cotransporters and the renal outer medullary K+ channel ROMK and Cl(-) channel SLC26A9. To evaluate the effect of WNK3 on TRPV5 t:700;'>TRPV5, a renal epithelial Ca2+ channel that serves as a gatekeeper for active Ca2+ reabsorption, WNK3 and TRPV5 were coexpressed in Xenopus laevis oocytes and the function and expression of TRPV5 were subsequently examined. An 82.7 +/- 7.1% increase in TRPV5-mediated Ca2+ uptake was observed when WNK3 was coexpressed. A similar increase in TRPV5-mediated Na+ current was observed with the voltage-clamp technique. WNK3 also enhanced Ca2+ influx and Na+ current mediated by TRPV6, which is the closest homolog of TRPV5 that mediates active intestinal Ca2+ absorption. The kinase domain of WNK3 alone was sufficient to increase TRPV5-mediated Ca2+ transport, and the positive regulatory effect was abolished by the kinase-inactive D294A mutation in WNK3, indicating a kinase-dependent mechanism. The complexly glycosylated TRPV5 that appears at the plasma membrane was increased by WNK3. The exocytosis of TRPV5 was increased by WNK3, and the effect of WNK3 on TRPV5 was abolished by the microtubule inhibitor colchicine. The increased plasma membrane expression of TRPV5 was likely due to the enhanced delivery of mature TRPV5 to the plasma membrane from its intracellular pool via the secretory pathway. These results indicate that WNK3 is a positive regulator of the transcellular Ca2+ transport pathway. | 18768590 | 2008-09-01 |
