Polarized trafficking of E-cadherin in epithelial cells.

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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.