Chapter 21 – Calbindin-D28K and Calbindin-D9K and the Epithelial Calcium Channels TRPV5 and TRPV6

Abstract We once viewed calbindin-D 28K and calbindin-D 9K as exclusively vitamin D-dependent proteins. It is now evident that the calbindins are not under the exclusive regulatory control of 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 . Calbindin-D 28K and calbindin-D 9K 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-D 28K interacts with TRPV5 and regulates its activity, suggesting a role for calbindin-D 28K as a modulator of calcium influx. Studies using calbindin-D 9k 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) 2 D 3 -mediated intestinal calcium absorption remain to be identified.