ENAMEL MATRIX PROTEIN INTERACTION

这项拟议工作的长期目标是描述蛋白质之间的相互作用。 涉及釉质细胞外基质蛋白以及血浆中不可或缺的蛋白 成釉细胞的细胞膜，并表征这些相互作用如何调节釉质 队形。为了实现这一点，Biglycan，Cd63，Anxa2和Lamp1，以及 它们与主要的釉质基质蛋白的关系将被研究。这是一个假设 GRANT的应用是“涉及分泌的釉质基质蛋白的蛋白质-蛋白质相互作用和 成釉细胞的分泌面(托姆氏突起)在成釉细胞的形成中起着关键作用。 为了检验这一假设，我们提出了三个具体目标。 目的是：1)使用原位杂交和小鼠特异性抗体来定义时空 CD63、Anxa2和Lamp1在发育中的小鼠门牙中的表达 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 和釉质生物矿化的阶段；2)证明了蛋白质-蛋白质 釉质基质蛋白与Biglycan、CD63、Anxa2和 Lampl在体内发生并具有生理意义，并定义了最小结合 与釉原蛋白相互作用的CD63和Lamp1结构域；3)定义和干扰 受体介导的允许牙釉质基质表达水平的分子机制 Biglycan影响或控制釉原蛋白的表达水平，以及随后发生的事件 釉质生物矿化。从这项研究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，或仿生学。这些数据将对他们的其他用户至关重要 追求再生一颗完整的牙齿。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科蛋白的蛋白质相互作用。

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.