Trafficking of E-cadherin in epithelial cells.

E-钙粘蛋白是体内负责介导细胞间粘附的主要蛋白质之一。在发育过程中，E-钙粘蛋白对于建立上皮器官的细胞结构和维持成人上皮功能是必不可少的。在这种情况下，E-钙粘蛋白的作用是建立和维持上皮细胞的极性。E-钙粘蛋白也是一种强大的肿瘤抑制因子，E-钙粘蛋白表达或功能的丧失是转移和癌症侵袭的主要事件。上皮细胞表面的蛋白质必须被分类和运输，或运输到不同的膜结构域。例如，E-钙粘蛋白必须被运输到细胞的侧域，以便在细胞-细胞粘附中起作用。我们最近发现，细胞表面的E-钙粘蛋白是重新内化，并通过一个途径，这是准备作出贡献的细胞粘附的调节循环回到表面。我们提出的研究旨在揭示新合成的E-钙粘蛋白和回收E-钙粘蛋白是如何运输的，哪些分子和哪些囊泡载体完成这种运输。E-钙粘蛋白具有特定的氨基酸，作为其分选和运输的靶向信号;我们最近发现了一个这样的信号，现在将寻找负责其内吞作用的信号。使用E-cadherin的特殊工程突变体，我们还将研究其他蛋白质，与E-cadherin相互作用，在其运输过程中进行分选和调节。其中之一是多囊蛋白，一种在常见遗传性肾病中突变的蛋白质。深入了解这种疾病和正常的肾上皮功能将出现从这项工作。越来越多的了解E-钙粘蛋白的功能和调节对于上皮器官的健康以及控制和预防癌症是必不可少的。

E-cadherin is one of the major proteins responsible for mediating cell-to-cell adhesion in the body. During development, E-cadherin is essential for establishing the cellular architecture of epithelial organs and for maintaining epithelial function in the adult. In this context, E-cadherin acts to establish and maintain the polarity of epithelial cells. E-cadherin is also a powerful tumour suppressor and the loss of E-cadherin expression or function is a primary event in metastasis and cancer invasion. Proteins at the surface of epithelial cells must be sorted and trafficked, or transported, to different membrane domains. E-cadherin, for instance, must be trafficked to the lateral domain of cells in order to function in cell-cell adhesion. We recently discovered that cell surface E-cadherin is re-internalized and recycled back to the surface via a pathway that is poised to contribute to the regulation of cell adhesion. Our proposed studies aim to reveal how newly-synthesized E-cadherin and recycling E-cadherin are trafficked, which molecules and which vesicle carriers accomplish this transport. E-cadherin has specific amino acids that act as targeting signals for its sorting and trafficking; we have recently identified one such signal and will now seek the signal responsible for its endocytosis. Using specifically engineered mutants of E-cadherin we will also study other proteins that interact with E-cadherin during its trafficking for sorting and regulation. One of these is polycystin, a protein that is mutated in a common inherited kidney disease. Insights into this disease and normal kidney epithelial function will emerge from this work. A growing understanding of E-cadherin function and regulation is essential for the health of epithelial organs and for controlling and preventing cancer.