ADHESIVE JUNCTIONS AND SIGNAL TRANSDUCTION IN DROSOPHILA

所提出的实验旨在了解 果蝇armadillo基因在组织细胞间粘附中作用 连接，并介导无翅细胞间的转导 信号了 果蝇模式形成研究的趋同性 并进入生物化学和细胞生物学的粘附连接， 哺乳动物细胞导致了一个模型的发展， 发展中的粘合剂连接。 我们的实验将检验这个模型。 细胞粘附被认为在正常的细胞粘附中起重要作用。 发育，以及在发育过程中发生的细胞行为变化， 恶性转化 犰狳基因的鉴定 斑珠蛋白和β-连环蛋白的果蝇同系物， 是不同哺乳动物粘附点的关键成分， 这些连接点的功能都有遗传学上的切入点 只有少数已知参与细胞相互作用的基因， 果蝇的分子特征。 的知识水平 犰狳基因产物的分子本质， 在生物化学水平上进行研究， 除了最初的分子分析， 犰狳蛋白的细胞生物学 具体目标开始，确定是否犰狳蛋白 与其他蛋白质结合，就像它的哺乳动物同系物一样。 将使用生化和遗传方法来识别，并 最终克隆这些犰狳相关蛋白。 的性质 犰狳蛋白修饰将被确定，和其他的作用， 片段极性基因在此修改检查。 的功能 我们将通过研究突变蛋白质的功能来探索犰狳 在果蝇和异源哺乳动物组织培养中， 系统 最后，我们将从形态学上表征细胞间 粘附连接，并检查是否犰狳突变破坏他们的 形成或结构。

The proposed experiments are directed toward understanding the role of the armadillo gene of Drosophila in organizing cell-cell adhesive junctions, and in mediating transduction of the wingless intercellular signal. The convergence of research into pattern formation in Drosophila and into the biochemistry and cell biology of adhesive junctions in mammalian cells has led to the development of a model for the role of adhesive junctions in development. Our experiments will test this model. Cell adhesion has been thought to play an important role both in normal development, and in the changes in cell behavior that occur during malignant transformation. The identification of the armadillo gene as the Drosophila homolog of plakoglobin and beta-catenin, molecules that are key components of different mammalian adhesive junctions, provides us with a genetic entrypoint into the function of these junctions. Only a few of the genes known to be involved in cell interactions in Drosophila have been molecularly characterized. The level of knowledge of the molecular nature of the armadillo gene product, and the tools which exist for studying it on a biochemical level, position us to move beyond the initial molecular analysis to examine the biochemistry and cell biology of armadillo protein. The specific aims begin with determining whether armadillo protein associates with other proteins, as do its mammalian homologs. Biochemical and genetic approaches will be used to identify, and ultimately clone these armadillo -associated proteins. The nature of armadillo protein modification will be determined, and the role of other segment polarity genes in this modification examined. The function of armadillo will be explored by examining the function of mutant proteins both in Drosophila and in the heterologous mammalian tissue culture system. Finally, we will morphologically characterize intercellular adhesive junctions, and examine whether armadillo mutations disrupt their formation or structure.