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Blood calcium concentration is maintained within a narrow range despite large variations in dietary input and body demand. The Transient Receptor Potential ion channel TRPV5 has been implicated in this process. We report here that TRPV5 is stimulated by the mammalian hormone klotho. Klotho, a beta-glucuronidase, hydrolyzes extracellular sugar residues on(More)
PURPOSE OF REVIEW Recent studies have greatly increased our knowledge concerning the regulation of renal calcium handling. This review focuses on newly identified calciotropic factors present in the pro-urine and the mechanisms by which they control the transient receptor potential channel vanilloid subtype 5 (TRPV5) which forms the gatekeeper of active(More)
The transient receptor potential vanilloid 5 (TRPV5) channel determines urinary Ca(2+) excretion, and is therefore critical for Ca(2+) homeostasis. Interestingly, mice lacking the serine protease tissue kallikrein (TK) exhibit robust hypercalciuria comparable to the Ca(2+) leak in TRPV5 knockout mice. Here, we delineated the molecular mechanism through(More)
BACKGROUND Kidney stone formation is a major socioeconomic problem in humans, involving pain, recurrent treatment and renal insufficiency. As most renal precipitates contain calcium as a major component, hypercalciuria is the main risk factor for renal stone formation. Different forms of hypercalciuria can be classified, which primarily arise from defects(More)
Extracellular pH has long been known to affect the rate and magnitude of ion transport processes among others via regulation of ion channel activity. The Ca(2+)-selective transient receptor potential vanilloid 5 (TRPV5) channel constitutes the apical entry gate in Ca(2+)-transporting cells, contributing significantly to the overall Ca(2+) balance. Here, we(More)
TRPM6 and its closest relative TRPM7 are members of the Transient Receptor Potential Melastatin (TRPM) subfamily of cation channels and are known to be Mg2+ permeable. By aligning the sequence of the putative TRPM6 pore with the pore sequences of the other subfamily members, we located in the loop between the fifth and the sixth transmembrane domain, a(More)
The epithelial Ca(2+) channels TRPV5 and TRPV6 constitute the apical Ca(2+) entry pathway in the process of active Ca(2+) (re)absorption. By yeast two-hybrid and glutathione S-transferase pulldown analysis we identified RGS2 as a novel TRPV6-associated protein. RGS proteins determine the inactivation kinetics of heterotrimeric G-protein-coupled receptor(More)
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(More)
The transient receptor potential vanilloid channels 5 and 6 (TRPV5/6) are the most Ca(2+)-selective channels within the TRP superfamily of ion channels. These epithelial Ca(2+) channels are regulated at different intra- and extracellular sites by the feedback response of Ca(2+) itself, calciotropic hormones, and by TRPV5/6-associated proteins. In the(More)
The extracellular Ca(2+)-sensing receptor (CaR) is a key-player in plasma Ca(2+) homeostasis. It is essentially expressed in the parathyroid glands and along the kidney nephron. The distal convoluted tubules (DCT) and connecting tubules (CNT) in the kidney are involved in active Ca(2+) reabsorption, but the function of the CaR has remained unclear in these(More)