Abstract
We once viewed calbindin-D28K and calbindin-D9K as exclusively vitamin D-dependent proteins. It is now evident that the calbindins are not under the exclusive regulatory control of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3. Calbindin-D28K and calbindin-D9K are present in many different tissues and may serve many different functions. Accordingly, the regulation of these calcium-binding proteins is varied and quite complex. The calcium-selective epithelial calcium channels, transient receptor potential vanilloid 5 and 6 (TRPV5 and TRPV6), are colocalized with calbindin in the kidney and intestine, respectively. Studies in TRPV5 knockout (KO) mice have indicated that TRPV5 is important for renal calcium reabsorption. Calbindin-D28K interacts with TRPV5 and regulates its activity, suggesting a role for calbindin-D28K as a modulator of calcium influx. Studies using calbindin-D9k and TRPV6 KO mice suggest that in the KO mice there is compensation by another calcium channel or protein and that other factors involved in 1,25(OH)2D3-mediated intestinal calcium absorption remain to be identified.