CELL/CELL JUNCTION, STRUCTURE AND DYNAMICS IN ORAL EPITHELIUM

细胞-细胞和细胞-底物的可逆调节 如果认为粘合剂接触在制造过程中起重要作用， 上皮组织重塑 在迁徙阶段， 重塑，细胞数量的急剧减少， 称为桥粒的连接已经被报道。 但 桥粒消失或重组的机制 在这个过程中是未知的。 一个重塑的例子， 牙周病是牙周病的一种常见病。 美国的主要健康问题，是外来移民 连接上皮沿着牙齿表面， 牙龈结缔组织溶解。 为了解 桥粒调节如何影响口腔上皮细胞 迁移，调节桥粒的分子机制 组装和溶解必须使用定义明确的 体外和细胞培养模型。 在这个项目中，我们将继续我们的 努力定义蛋白质-蛋白质相互作用的桥粒， 我们没有研究口腔粘膜中粘附连接是如何被调节的， 上皮细胞培养物。 具体目标是：1）确定 蛋白质-蛋白质相互作用参与建立结构 的桥粒斑，并确保分离 桥粒和粘附连接成分分成不同的 膜结构域，2）研究细胞间连接 动力学和相关细胞骨架的作用， 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 口腔上皮细胞的遗传操作，3）检查 牙龈中存在的蛋白酶的贡献 微环境对结溶解的影响，并确定 特异性桥粒钙粘蛋白是这些蛋白酶的底物。 这些研究将与其他项目领导人广泛交流 谁将提供试剂（即，来自Goldman博士的IFAP 300， 层粘连蛋白-5肽，来自Jones和Stack博士）和专业知识 （用于活细胞的荧光标记探针的产生 观察，戈德曼博士;酶谱分析，斯塔克博士）。 这项工作将提供重要的洞察机制， 其中细胞-细胞粘附连接被组装和调节， 迁移的口腔上皮细胞，并将提供基础， 治疗方法的设计，以遏制进展 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.