Regulation of Adherens Junction Remodeling in Drosophila

果蝇粘附连接重塑的调控

• 批准号: 7112498
• 负责人: Jeremiah F Roeth
• 金额: $ 3.95万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7112498
• 关键词: Drosophilidae; cadherins; cell adhesion; cell adhesion molecules; cytoskeletal proteins; cytoskeleton; embryogenesis; endocytosis; histogenesis; intercellular connection; intracellular transport; invertebrate embryology; microtubules; postdoctoral investigator

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.

描述（由申请人提供）：粘附连接（AJ）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。哺乳动物细胞研究表明，AJ 的细胞内运输可调节粘附；然而，正常发育和组织稳态过程中这一过程的调节很大程度上未知。我们假设 AJ 重塑通过 AJ 成分的定向运输与形态发生和组织维持紧密耦合。此外，我假设 AJ 在有丝分裂过程中通过与细胞骨架的调节相互作用进行修饰和重新组装。我将研究果蝇胚胎中 AJ 蛋白的细胞内转运机制。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 AJ 内吞作用的潜在调节因子，并研究微管和运动蛋白在 AJ 转运中的假定作用。最后，我将利用从这些研究中获得的信息来制定和测试有丝分裂和胚胎发育过程中协调 AJ 重塑的模型。