DESMOCOLLINS AND CELLULAR ADHESION

该项目的长期目标是描述 细胞间黏附中的桥粒连结蛋白。Desmocolin是主要的糖蛋白 桥粒的组成和黏附破坏的靶标 严重水泡患者血清中存在抗体 寻常型天疱疮。从结构上讲，它们构成了 钙粘附素是一种细胞间黏附和识别分子家族。 Desmocolin以一系列组织特异性异构体的形式出现，由 另一种拼接。这些异构体的确切作用尚不清楚。 假设它们对粘连机制是必不可少的。 桥粒可能在细胞识别、细胞骨架等方面发挥作用 细胞-细胞初始接触的结合和接受与转导 信号。 桥粒游离素亚型在成体组织和成体组织中的分布 在胚胎发育过程中将通过免疫化学和聚合酶链式反应进行检查 确定表达模式是否兼容的技术 在形态发生中起作用。异构体与蛋白质的相互作用 将通过以下方式检查其他连接组件和蛋白激酶 共沉淀和体外结合试验，以确定它们是否 在信号转导和/或细胞骨架结合中发挥作用。类似 技术将被用来定义它们在平面上的关联 膜是同型的或异型的。居间的序列 以及调节这些分子的结合亲和力的研究将通过 野生型和重组结缔组织黏附素对小鼠免疫功能的影响 支持细胞间的黏附和破坏黏附的能力 抗体干扰这一过程。这些序列控制 针对邻近BUT的桥粒连结蛋白和钙粘附素的特异性靶向 生物化学上不同的膜结构域将通过研究 这些分子嵌合体的连接定位。这些研究 应该为结缔组织的具体作用提供新的见解 细胞间黏附与水疱病的发病机制 寻常型天疱疮。

The long term goal of this project is to characterize the role of desmocollins in cell-cell adhesion. Desmocollins are major glycoprotein components of the desmosome, and the targets of adhesion-disrupting antibodies present in the sera of patients with the severe blistering disease pemphigus vulgaris. Structurally, they form a distinct subset of the cadherins, a family of cell-cell adhesion and recognition molecules. Desmocollins occur as a number of tissue-specific isoforms generated by alternative splicing. The precise roles of these isoforms are not known. It is hypothesized that they are essential to the adhesive mechanism of the desmosome and may play a role in cellular recognition, cytoskeletal binding and the reception and transduction of initial cell-cell contact signals. The distribution of the desmocollin isoforms in both adult tissues and during embryonic development will be examined immunochemically and by PCR techniques to determine whether the pattern of expression is compatible with a role in morphogenesis. The interactions of the isoforms with other junctional components and with kinases will be examined, by co-precipitation and in vitro binding assays, to identify whether they function in signal transduction and/or cytoskeletal binding. Similar techniques will be used to define whether their association in the plane of the membrane is homotypic or heterotypic. The sequences that mediate and regulate the binding affinity of these molecules will be studied by comparing the capacity of wild type and recombinant desmocollins to support cell-cell adhesion and the ability of adhesion disrupting antibodies to interfere with this process. The sequences that govern the specific targeting of desmocollins and cadherins to their neighboring but biochemically distinct membrane domains will be studied by examining the junctional localization of chimeras of these molecules. These studies should provide new insights into the specific role of the desmocollins in cell-cell adhesion as well as the pathogenesis of the blistering disease pemphigus vulgaris.