Exclusion of all three calbindins from a calcium-ferry role in rat enamel cells.

It is widely accepted that healthy enamel formation depends on a steady supply of calcium, yet only fragmentary understanding exists about the mechanisms underlying transepithelial calcium transport. Several lines of evidence indicate that calcium principally follows a transcellular route, which classically is thought to be facilitated by cytosolic calcium-binding proteins termed calbindins. In enamel cells, however, this 'calcium-ferry' dogma appears to fail as we previously found that the major calbindin in murine enamel cells (calbindin-28 kDa) was down-regulated during the peak period of calcium transport and enamel was formed normally in mice lacking calbindin-28 kDa. It remains to be clarified whether the two other known calbindins could function as calcium ferries instead. This study used biochemical and proteomic approaches to obtain definitive identification and quantification of the 30-kDa calbindin (calretinin) and calbindin-9 kDa (S100-G) in enamel epithelium from rat. By establishing that both of these calbindins contribute insufficient calcium capacities in molars and incisors, our results render the calcium-ferry dogma untenable. Of significance to enamel defects and dental bioengineering, these findings support other evidence for an alternative organelle-based mode of calcium transport (calcium transcytosis) and also implicate S100-G/calbindin-9 kDa, but not calretinin, in a calcium-signaling role during enamel maturation.