CELL/CELL JUNCTION, STRUCTURE AND DYNAMICS IN ORAL EPITHELIUM

细胞-细胞和细胞-衬底的可逆调制 粘性接触如果被认为在 上皮组织重塑。在迁徙阶段 重塑，细胞数量的急剧减少 已有报道称连接为桥粒。然而， 桥粒消失或重组的机制 在这个过程中都是未知的。改建的一个例子就是 有助于牙周病的进展，这是一种 美国的主要健康问题是外来移民 牙面交界处的上皮细胞 牙周结缔组织溶解。为了理解 桥粒的调节对口腔上皮细胞的影响 迁移--调节桥粒的分子机制 组装和溶解必须使用在 体外和细胞培养模型。在这个项目中，我们将继续我们的 努力确定桥粒和蛋白质之间的相互作用 I don‘我不知道口腔中粘连连接是如何调节的 上皮细胞培养。具体目标是：1)确定 蛋白质-蛋白质相互作用参与结构的建立 桥粒斑块和确保分离 桥粒和粘连连接成分形成截然不同的 膜结构域，2)研究细胞间连接 相关细胞骨架的动力学和作用 口腔上皮细胞迁移过程中的细胞外基质 细胞，使用活细胞观察和分子生物学相结合 口腔上皮细胞的遗传操作，3)检查 牙龈中存在的蛋白水解酶的作用 微环境对结合部溶解的影响 特定的桥粒钙粘附素是这些酶的底物。 这些研究将与其他项目负责人广泛接触 谁将提供试剂(即戈德曼博士的IFAP300和 来自Jones博士和Stack博士的层粘连蛋白-5肽)和专业知识 (活细胞荧光标记探针的研制 观察，戈德曼博士；酶谱分析，斯塔克博士)。 这项工作将通过以下方式提供对机制的重要见解 细胞-细胞黏附连接在哪些区域组装和调节 迁移口腔上皮细胞，并将为 设计治疗方法以遏制癌症的进展 牙周病。

The reversible modulation of both cell-cell and cell-substrate adhesive contacts if thought to play an important role during epithelial tissue remodeling. During the migratory phase of remodeling, a dramatic reduction in the number of cell-cell junctions known as desmosomes has been reported. However, the mechanisms governing desmosome disappearance or reassembly during this process are unknown. One example of remodeling that contributes to the progression of periodontal disease, which is a major health problem in the U.S., is the inward migration of junctional epithelium along the tooth surface that occurs following dissolution of gingival connective tissue. In order to understand how modulation of desmosomes may impact on oral epithelial cell migration, the molecular mechanisms that regulate desmosome assembly and dissolution must be elucidated using well-defined in vitro and cell culture models. In this project we will continue our efforts to define protein-protein interactions in the desmosome and t investigate how adhesive junctions are modulated in oral epithelial cell cultures. The specific aims are: 1) To determine the protein-protein interactions involved in establishing the structure of the desmosomal plaque and ensuring segregation of desmosomal and adherens junction components into distinct membrane domains, 2) To investigate intercellular junction dynamics and the role of the associated cytoskeleton and underlying extracellular matrix during migration of oral epithelial cells, using a combination of live cell observations and molecular genetic manipulation of oral epithelial ells, 3) To examine the contribution of proteinases present in the gingival microenvironment to junction dissolution and to define whether specific desmosomal cadherins are substrates for these proteinases. These studies will interface extensively with other project leaders who will provide reagents (i.e., IFAP300 from Dr. Goldman and laminin-5 peptides from Drs. Jones and Stack) and expertise (generation of fluorescently labeled probes for living cell observations, Dr. Goldman; zymographic analysis, Dr. Stack). This work will provide important insights into mechanisms by which cell-cell adhesive junctions are assembled and modulated in migrating oral epithelial cells, and will provide a basis for the design of therapeutic approached to curb the progression of periodontal disease.