Hubbard Michael J, McHugh Nicola J, Mangum Jonathan E
Department of Biochemistry, University of Otago, Dunedin, New Zealand.
Eur J Oral Sci. 2011 Dec;119 Suppl 1:112-9. doi: 10.1111/j.1600-0722.2011.00890.x.
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.
人们普遍认为，健康的牙釉质形成依赖于钙的稳定供应，但对于跨上皮钙转运的潜在机制，目前仅有碎片化的认识。多项证据表明，钙主要通过跨细胞途径运输，传统观点认为，这一过程由被称为钙结合蛋白的胞质钙结合蛋白促进。然而，在牙釉质细胞中，这一“钙摆渡”理论似乎并不成立，因为我们之前发现，小鼠牙釉质细胞中的主要钙结合蛋白（28 kDa钙结合蛋白）在钙转运高峰期表达下调，且在缺乏28 kDa钙结合蛋白的小鼠中，牙釉质仍能正常形成。另外两种已知的钙结合蛋白是否能替代其发挥钙摆渡的功能，仍有待阐明。本研究采用生化和蛋白质组学方法，对大鼠牙釉质上皮中的30 kDa钙结合蛋白（钙视网膜蛋白）和9 kDa钙结合蛋白（S100-G）进行了明确鉴定和定量分析。通过证实这两种钙结合蛋白在磨牙和切牙中的钙转运能力均不足，我们的研究结果表明“钙摆渡”理论站不住脚。这些发现对于牙釉质缺陷和牙齿生物工程具有重要意义，它们支持了另一种基于细胞器的钙转运模式（钙转胞吞作用）的其他证据，并且还表明S100-G/9 kDa钙结合蛋白而非钙视网膜蛋白在牙釉质成熟过程中发挥钙信号作用。
