PDF(Pubmed)
Abstract：
Extracellular matrix proteins play crucial roles in the formation of mineralized tissues like bone and teeth via multifunctional mechanisms. In tooth enamel, ameloblastin (Ambn) is one such multifunctional extracellular matrix protein implicated in cell signaling and polarity, cell adhesion to the developing enamel matrix, and stabilization of prismatic enamel morphology. To provide a perspective for Ambn structure and function, we begin this review by describing dental enamel and enamel formation (amelogenesis) followed by a description of enamel extracellular matrix. We then summarize the established domains and motifs in Ambn protein, human amelogenesis imperfecta cases, and genetically engineered mouse models involving mutated or null Ambn. We subsequently delineate in silico, in vitro, and in vivo evidence for the amphipathic helix in Ambn as a proposed cell-matrix adhesive and then more recent in vitro evidence for the multitargeting domain as the basis for dynamic interactions of Ambn with itself, amelogenin, and membranes. The multitargeting domain facilitates tuning between Ambn-membrane interactions and self/co-assembly and supports a likely overall role for Ambn as a matricellular protein. We anticipate that this review will enhance the understanding of multifunctional matrix proteins by consolidating diverse mechanisms through which Ambn contributes to enamel extracellular matrix mineralization.
摘要：
细胞外基质蛋白通过多功能机制在骨骼和牙齿等矿化组织的形成中起着至关重要的作用。在牙釉质中，成釉细胞蛋白（Ambn）是一种涉及细胞信号传导和极性的多功能细胞外基质蛋白，细胞粘附在发育中的釉质基质上，棱柱形釉质形态的稳定。为Ambn的结构和功能提供视角，我们从描述牙釉质和牙釉质形成（牙釉质发生）开始这篇综述，然后描述牙釉质细胞外基质。然后，我们总结了Ambn蛋白中已建立的结构域和基序，人类釉质发生不全症病例，和涉及突变或无效Ambn的基因工程小鼠模型。我们随后在计算机上描绘，在体外，以及Ambn中两亲性螺旋作为拟议的细胞-基质粘合剂的体内证据，然后是多靶向域作为Ambn与自身动态相互作用的基础的最新体外证据，釉原蛋白，和膜。多靶向结构域促进Ambn-膜相互作用和自/共组装之间的调节,并且支持Ambn作为基质细胞蛋白的可能的总体作用。我们预计，这篇综述将通过巩固Ambn有助于釉质细胞外基质矿化的多种机制来增强对多功能基质蛋白的理解。
