ENAMEL MATRIX PROTEIN INTERACTION

这项工作的长期目标是表征蛋白质-蛋白质相互作用 包括釉质细胞外基质蛋白，以及血浆中的蛋白质 膜的成釉细胞，并表征这些相互作用如何调节釉质 阵为了实现这一点，研究了双糖链蛋白聚糖、Cd 63、Anxa 2和Lampl的分子生物化学，以及 将研究它们与主要釉质基质蛋白的关系。这个假设 授予申请是“蛋白质-蛋白质相互作用涉及分泌的釉质基质蛋白质和 成釉细胞的分泌表面（Tomes'prostheses）在成釉细胞的形成中起关键作用。 搪瓷棱柱结构。“为了验证这一假设，我们提出了三个具体目标。这些 是：1）定义，使用原位杂交和小鼠特异性抗体， 在小鼠发育中的切牙内Cd 63、Anxa 2和Lampl的表达模式，以及 将这些表达谱与它们各自的配体（釉质基质蛋白）的表达谱相关联 伴侣），和釉质生物矿化的阶段; 2）证明蛋白质-蛋白质 先前鉴定的釉质基质蛋白和双糖蛋白聚糖、Cd 63、Anxa 2和 Lampl在体内发生并具有生理学意义，并定义最小结合 Cd 63和Lamp 1的结构域，使它们能够与釉原蛋白相互作用; 3）定义和破坏 受体介导的分子机制允许釉基质表达水平 双糖链蛋白聚糖影响或控制釉原蛋白表达水平，以及随后的 釉质生物矿化从这方面和相关研究中获得的知识可能会导致更好的 牙科和非牙科材料或仿生材料。这些数据对其他人来说至关重要， 来再生一整颗牙齿。为了让牙齿再生成为现实，蛋白质- 必须知道和理解涉及关键牙齿蛋白质的蛋白质相互作用。

The long-term goal of this proposed work is to characterize protein-protein interactions involving the enamel extracellular matrix proteins, as well as proteins integral to the plasma membrane of ameloblast cells, and characterize how these interactions regulate enamel formation. To achieve this the molecular biochemistry of biglycan, Cd63, Anxa2 and Lampl, and their relationship to the major enamel matrix proteins, will be studied. The hypothesis of this grant application is "protein-protein interactions involving secreted enamel matrix proteins and the secretory surface of ameloblast cells (Tomes' processes) play a key role in the formation of the enamelprismatic structure." To test this hypothesis we propose three specific aims. These are to: 1) define, using in situ hybridization and mouse-specific antibodies, the spatiotemporal expression patterns for Cd63, Anxa2 and Lampl within the murine developing incisor tooth, and relate these expression profiles to those of their respective ligand (enamel matrix protein partner), and the stages of enamel biomineralization; 2) demonstrate that the protein-protein interactions previously identified for the enamel matrix proteins and biglycan, Cd63, Anxa2 and Lampl occur in vivo and have physiological significance, and to define the minimal binding domains of Cd63 and Lampl that enable their interaction with amelogenin; 3) define and disrupt the receptor-mediated molecular mechanism that permits the enamel matrix expression levels of biglycan to influence or control amelogenin expression levels, and the subsequent events of enamel biomineralization. Knowledge gained from this and related studies may lead to better dental and non-dental materials, or biomimetics. This data will be critical to others in their pursuits to regenerate an entire tooth. For tooth regeneration to become a reality, the protein- protein interactions involving the key dental proteins must be known and understood.