Polarized trafficking of E-cadherin in epithelial cells.

上皮细胞中 E-钙粘蛋白的极化运输。

• 批准号: nhmrc : 401592
• 负责人: A/Pr Rohan Teasdale
• 金额: $ 34.38万
• 依托单位: The University of Queensland
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/polarized-trafficking-e-epithelial-cells/97777
• 关键词: Polarized; trafficking; cadherin; epithelial; cells.

The cell adhesion protein E-cadherin is expressed in all epithelial tissues of the body where it has essential functions during development and in the adult in establishing and maintaining polarized cell monolayers. E-cadherin is also a vital tumour suppressor, its normal function guarantees that cells or even early tumours cannot metastasise; in contrast E-cadherin is always lost or malfunctions in malignant tumours. Earlier studies showed that E-cadherin is constantly moved, or trafficked, to and from the surface of epithelial cells. This trafficking has dual roles, firstly in delivering newly-made E-cadherin to the surface where it functions and secondly, in regulating its adhesive function. Our research in this project is focussed on the molecules and intracellular compartments that control the delivery of E-cadherin to the cell surface. E-cadherin must be sorted in order to be delivered to the correct side of the cell. Having previously discovered the sorting signal in E-cadherin, we will now identify the cognate adaptor protein(s) that accomplish this sorting. New imaging techniques allow us to study protein trafficking inside live cells. Such studies have recently revealed that E-cadherin passes through a recycling endosome compartment on its way to the cell surface. This unexpected route, and the structure and role of the recycling endosome will now be studied in detail in live cells. Finally we will compare the sorting and trafficking of E-cadherin with the closely-related N-cadherin protein, to determine whether there are inherent differences in their trafficking that could explain their opposite roles in tumour cells, where N-cadherin is substituted for E-cadherin and allows metastatic behaviour. These studies will provide important information for understanding the adhesive and tumour suppressive roles of E-cadherin. In addition our findings will generate information fundamental to our understanding of cell polarity and protein sorting.

细胞粘附蛋白E-钙粘蛋白在身体的所有上皮组织中表达，在发育期间和在成人中在建立和维持极化细胞单层中具有重要功能。E-cadherin也是一种重要的肿瘤抑制因子，其正常功能保证细胞甚至早期肿瘤不能转移;相反，E-cadherin在恶性肿瘤中总是丢失或功能障碍。早期的研究表明，E-钙粘蛋白是不断移动，或贩运，从上皮细胞的表面。这种运输具有双重作用，首先是将新产生的E-钙粘蛋白运送到其发挥作用的表面，其次是调节其粘附功能。我们在这个项目中的研究集中在控制E-钙粘蛋白传递到细胞表面的分子和细胞内隔室。E-cadherin必须被分选，以便被递送到细胞的正确侧。先前已经发现了E-钙粘蛋白中的分选信号，我们现在将鉴定完成这种分选的同源衔接蛋白。新的成像技术使我们能够研究活细胞内的蛋白质运输。这些研究最近揭示，E-钙粘蛋白在其到达细胞表面的途中通过再循环内体隔室。这种意想不到的途径，以及再循环内体的结构和作用，现在将在活细胞中详细研究。最后，我们将比较E-钙粘蛋白的分选和运输与密切相关的N-钙粘蛋白蛋白，以确定是否有内在的差异，在他们的贩运，可以解释他们在肿瘤细胞中的相反作用，其中N-钙粘蛋白取代E-钙粘蛋白，并允许转移行为。这些研究将为理解E-cadherin的粘附和肿瘤抑制作用提供重要信息。此外，我们的发现将产生我们理解细胞极性和蛋白质分选的基本信息。