Regulation of Adherens Junction Remodeling in Drosophila

描述（由申请人提供）：粘附连接（AJs）是细胞间粘附的关键调节因子，因此在细胞自组装成复杂组织中发挥重要作用。AJ组装和分解之间的平衡可能在形态发生过程中受到调节。在哺乳动物细胞中的研究表明，AJs的细胞内运输调节粘附;然而，在正常发育和组织稳态过程中，这一过程的调节在很大程度上是未知的。我们推测，AJ重塑是紧密耦合到形态发生和组织维护通过AJ组件的直接贩运。此外，我假设AJs的修改和重新组装在有丝分裂过程中的调节与细胞骨架的相互作用。我将研究AJ蛋白在果蝇胚胎中的胞内转运机制。我将对DE-钙粘蛋白胞质结构域进行诱变，以确定影响AJ细胞表面稳定性的区域。我将定义潜在的调节AJ内吞作用，我将检查微管和马达蛋白在AJ运输的假定作用。最后，我将利用这些研究中获得的信息，制定和测试模型的协调AJ重塑在有丝分裂和胚胎发育。

DESCRIPTION (provided by applicant): Adherens junctions (AJs) are key regulators of intercellular adhesion and thus play an important role in the self-assembly of cells into complex tissues. The balance between AJ assembly and disassembly is likely to be regulated during mophogenesis. Studies in mammalian cells suggest that the intracellular trafficking of AJs modulates adhesion; however, the regulation of this process during normal development and tissue homeostasis is largely unknown. We hypothesize that AJ remodeling is tightly coupled to morphogenesis and tissue maintenance via the directed trafficking of AJ components. Furthermore, I hypothesize that AJs are modified and reassembled during mitosis by regulated interactions with the cytoskeleton. I will investigate the mechanism of the intracellular transport of AJ proteins in Drosophila embryos. I will mutagenize the DE-cadherin cytoplasmic domain to determine regions that affect AJ cell surface stability. I will define potential regulators of AJ endocytosis, and I will examine the putative role of microtubules and motor proteins in AJ transport. Finally, I will use the information gained from these studies to formulate and test models of coordinated AJ remodeling during mitosis and embryonic development.