Concerted action of associated proteins in the regulation of TRPV5 and TRPV6

Ca²⁺ is an essential ion in all organisms and many physiological functions in the body rely on the exact maintenance of the Ca²⁺ balance. The epithelial Ca²⁺ channels TRPV5 [TRP (transient receptor potential) vanilloid 5] and TRPV6 are the most Ca²⁺-selective members of the TRP superfamily and are generally considered as the gatekeepers of Ca²⁺ entry across epithelia. TRPV5 is involved in Ca²⁺ reabsorption from pro-urine, while TRPV6 has an essential role in intestinal Ca²⁺ 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 Ca²⁺ 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 Ca²⁺ influx at the luminal entry gate.