ASPECTS OF CADHERIN/CATENIN COMPLEXES

上皮组织的细胞表现出紧密的细胞间相互作用 是由包括粘附素在内的各种细胞结构介导的 连接、桥粒、缝隙连接和紧密连接。这些细胞-细胞 缔合不仅在组织的形成中很重要，而且 同样重要的是在整个生命周期中保持其完整性 有机体。 一种名为钙粘附素的蛋白质家族已被证明可以调节钙- 依赖细胞黏附。钙粘附素的表达受发育调节 并与形态发生事件相关联，表明这些粘连 分子对于正常发育是必不可少的。此外，它一直是 提示钙粘素或钙粘附素功能下调可能 有助于癌症的转移性扩散。钙粘附素具有很高的 保守的细胞质结构域，与细胞内的 细胞骨架。这种相互作用对钙粘附素的调节至关重要 粘附力。已鉴定出几种蛋白质，称为连环蛋白，它们是 与钙粘附素有关。连环蛋白被认为起着中介作用 细胞骨架与钙粘附素的相互作用，从而连接 细胞骨架与质膜的结合；2)调节细胞的黏附活性。 钙粘附素。 这个项目的目标是加深我们对 钙粘附素和连接素在细胞相互作用中的作用 并确定钙粘附素/连环蛋白复合体与结构的关系 我们知道这是一个附着点。 该项目的具体目标是：1)确定 连环蛋白是与复合体结合所必需的，2)到 钙粘附素介导的细胞黏附的特征 一个钙粘附素；3)观察细胞中的钙粘附素/连环蛋白复合体 不形成典型的复合体，如成纤维细胞；以及4)确定 β-连环蛋白和γ-连环蛋白可以在钙粘附素中相互替代 很复杂。 我们将通过使用分子生物学来实现这些目标 生产各种蛋白质的截短版本的技术；通过使用 抑制各种蛋白质功能的抗体； 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.