E-Cadherin endocytosis in morphogenesis: recycling and growth factor induced uptake.

E-钙粘附素是一种细胞-细胞黏附蛋白，在所有上皮细胞中表达，在细胞极性的建立和发育过程中的组织构型中起着至关重要的作用。在成人中，E-钙粘附素起到维持上皮完整性的作用。E-钙粘附素也是一种重要的肿瘤抑制因子，保护细胞免受转移转化。我们早期的研究表明，E-钙粘素不断地移动或运输到上皮细胞表面或从上皮细胞表面转移出来。细胞表面E-钙粘附素的内吞或内化作用调节其在黏附中的作用。最近，我们和其他人已经证明，E-钙粘素内吞是对生长因子的反应，与激活的生长因子受体本身结合在一起。E-钙粘附素可以影响这些受体酪氨酸激酶的运输和信号传递。这种联合内吞作用是一种优雅的机制，可以同时下调细胞黏附和激活细胞生长和运动的信号。上皮细胞在组织构型或形态形成过程中的生长和分化关键依赖于这些内吞途径。我们的研究旨在明确参与E-钙粘素受体内吞作用的内体和细胞机制，此外，我们还将继续寻求初步发现，在不同生长因子的要求下，E-钙粘素内吞存在不同的途径和命运。我们将研究上皮囊形成和囊管形成过程中的内吞作用，作为哺乳动物形态发生的体外模型。这些研究将为理解E-钙粘附素在上皮形态发生过程中黏附和生长因子信号转导中的作用提供重要而新颖的信息。最终，这些发现将与上皮细胞的发育和癌症的预防相关。

E-cadherin is a cell-cell adhesion protein expressed in all epithelia with essential roles in establishing cell polarity and in tissue patterning during development. In the adult, E-cadherin functions to maintain epithelial integrity. E-cadherin is also a vital tumour suppressor, protecting cells against metastatic transformation. Our earlier studies showed that E-cadherin is constantly moved, or trafficked, to and from the surface of epithelial cells. The endocytosis or internalisation of cell surface E-cadherin serves to regulate its role in adhesion. More recently, we and others have shown that E-cadherin is endocytosed in response to growth factors, in conjunction with the activated growth factor receptors themselves. E-cadherin can influence the trafficking and signaling of these receptor tyrosine kinases. This joint endocytosis is an elegant mechanism for the simultaneous downregulation of cell adhesion and activation of signaling for cell growth and motility. The growth and differentiation of epithelial cells during tissue patterning or morphogenesis relies critically on these endocytic pathways. Our research is aimed at defining the endosomes and cellular machinery involved in E-cadherin-receptor endocytosis, moreover we will pursue initial findings suggesting that there are different pathways and fates for E-cadherin endocytosed at the behest of different growth factors. We will study endocytosis during the processes of epithelial cyst formation and tubulation of cysts as an in vitro model for mammalian morphogenesis. These studies will provide important and novel information for understanding the roles of E-cadherin in adhesion and in growth factor signaling during epithelial morphogenesis. Ultimately these findings will be of relevance to epithelial development and the prevention of cancer.