ASPECTS OF CADHERIN/CATENIN COMPLEXES

上皮组织的细胞显示出紧密的细胞间相互作用， 是由多种细胞结构介导的， 连接、桥粒、间隙连接和紧密连接。这些细胞 关联不仅在组织的形成中很重要， 同样重要的是，在整个生命周期中保持其完整性， 有机体 一个称为钙粘蛋白的蛋白质家族已被证明介导钙- 依赖细胞粘附。 钙粘蛋白的表达受发育调节 并与形态发生事件相关，表明这些粘附 分子对正常发育至关重要。 此外， 这表明钙粘蛋白或钙粘蛋白功能的下调可能 有助于癌的转移扩散。钙粘蛋白具有高度的 保守的胞质结构域，其与 细胞骨架这种相互作用对于钙粘蛋白介导 粘连已经鉴定了几种称为连环蛋白的蛋白质， 与钙粘蛋白相关。连环蛋白被认为是1）介导 细胞骨架与钙粘蛋白的相互作用，从而将 细胞骨架的质膜和2）调节粘附活性 钙粘蛋白 本项目的目标是进一步了解 细胞间相互作用中的钙粘蛋白和连环蛋白 并确定钙粘蛋白/连环蛋白复合物与结构的关系 我们称之为粘附连接。 该项目的具体目标是：1）确定 连环蛋白是与复合物结合所必需的，2） 表征钙粘蛋白介导的细胞粘附， 一种钙粘蛋白; 3）观察细胞中的钙粘蛋白/连环蛋白复合物， 不形成典型的复合物，如成纤维细胞;和4）确定是否 β-和γ-连环蛋白在钙粘蛋白中可以相互替代 复杂. 我们将通过使用分子生物学技术来实现这些目标。 技术来生产各种蛋白质的截短版本;通过使用 抑制各种蛋白质功能的抗体;以及 连接复合体的超微结构分析。

Cells of epithelial tissues display tight intercellular interactions which are mediated by a variety of cellular structures including adherens junctions, desmosomes, gap junctions and tight junctions. These cell-cell associations are not only important in the formation of a tissue but are equally important in maintaining its integrity throughout the life of the organism. A family of proteins, termed cadherins has been shown to mediate calcium- dependent cell adhesion. Cadherin expression is developmentally regulated and correlates with morphogenetic events suggesting that these adhesion molecules are essential to normal development. In addition, it has been suggested that down-regulation of cadherin or cadherin function may contribute to the metastatic spread of carcinomas. Cadherins have highly conserved cytoplasmic domains that interact indirectly with the cytoskeleton. This interaction is essential for the cadherin to mediate adhesion. Several proteins, termed catenins, have been identified that are associated with the cadherins. The catenins are thought to 1) mediate cytoskeletal interactions with the cadherins, thus linking the cytoskeleton to the plasma membrane and 2) regulate adhesive activity of the cadherins. The goals of this project are to further our understanding of the roles of cadherins and the catenins in the interaction of cells with one another and to determine how the cadherin/catenin complex relates to the structure we know as an adherens junction. The specific aims of this project are 1) to determine which domains of the catenins are necessary for association with the complex, 2) to characterize cadherin-mediated adhesion in cells that express more than one cadherin; 3) to look at cadherin/catenin complexes in cells that do not form typical complexes such as fibroblasts; and 4) to determine if beta- and gamma-catenin can substitute for one another in a cadherin complex. We will accomplish these aims by the use of molecular biological techniques to produce truncated versions of the various proteins; by using antibodies to inhibit function of the various proteins; and with ultrastructural analysis of junctional complexes.