Critical roles for WDR72 in calcium transport and matrix protein removal during enamel maturation.
Critical roles for WDR72 in calcium transport and matrix protein removal during enamel maturation.
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DOI：
10.1002/mgg3.143
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发表时间：
2015-07
影响因子：
2
通讯作者：
Simmer JP
中科院分区：
文献类型：
--
作者：
Wang SK;Hu Y;Yang J;Smith CE;Nunez SM;Richardson AS;Pal S;Samann AC;Hu JC;Simmer JP
WDR 72（WD重复蛋白72）缺陷导致常染色体隐性遗传性低成熟性釉质形成障碍。我们产生并表征了Wdr72敲除/lacZ敲入小鼠，以研究WDR72在釉质形成中的作用。在所有分析中，Wdr72杂合子小鼠形成的釉质与野生型釉质没有区别。没有WDR 72，釉质矿物质密度在成熟阶段早期增加，但很快停止。空釉质层只有野生型釉质的十分之一硬，并经历了快速磨损后喷发。尽管未能进一步矿化釉质沉积在分泌阶段，异位矿物质形成的釉质表面和渗透到覆盖的软组织。虽然釉质基质中的蛋白质被成功降解，但消化产物仍留在釉质内。WDR 72蛋白的相互作用组分析揭示了与网格蛋白相关蛋白的潜在相互作用，并参与成釉细胞内吞作用。成熟阶段的下颌切牙釉质没有甲基红染色，表明釉质没有酸化下皱褶端成釉细胞。成熟成釉细胞对釉质层的附着减弱，成釉细胞钙转运蛋白SLC24 A4不能沿着成釉细胞远端膜适当定位。在支持成釉细胞的乳头层中观察到较少的血管。成熟阶段成釉细胞的特异性WDR 72表达解释了在WDR 72缺失小鼠中釉质厚度和杆交叉（在分泌阶段期间建立）是正常的观察结果。我们的结论是，WDR 72服务的关键功能，特别是在成熟阶段的釉质，蛋白质去除和釉质矿化所需的。
Defects in WDR72 (WD repeat-containing protein 72) cause autosomal recessive hypomaturation amelogenesis imperfecta. We generated and characterized Wdr72-knockout/lacZ-knockin mice to investigate the role of WDR72 in enamel formation. In all analyses, enamel formed by Wdr72 heterozygous mice was indistinguishable from wild-type enamel. Without WDR72, enamel mineral density increased early during the maturation stage but soon arrested. The null enamel layer was only a tenth as hard as wild-type enamel and underwent rapid attrition following eruption. Despite the failure to further mineralize enamel deposited during the secretory stage, ectopic mineral formed on the enamel surface and penetrated into the overlying soft tissue. While the proteins in the enamel matrix were successfully degraded, the digestion products remained inside the enamel. Interactome analysis of WDR72 protein revealed potential interactions with clathrin-associated proteins and involvement in ameloblastic endocytosis. The maturation stage mandibular incisor enamel did not stain with methyl red, indicating that the enamel did not acidify beneath ruffle-ended ameloblasts. Attachment of maturation ameloblasts to the enamel layer was weakened, and SLC24A4, a critical ameloblast calcium transporter, did not localize appropriately along the ameloblast distal membrane. Fewer blood vessels were observed in the papillary layer supporting ameloblasts. Specific WDR72 expression by maturation stage ameloblasts explained the observation that enamel thickness and rod decussation (established during the secretory stage) are normal in the Wdr72 null mice. We conclude that WDR72 serves critical functions specifically during the maturation stage of amelogenesis and is required for both protein removal and enamel mineralization.