Trafficking of E-cadherin in epithelial cells.

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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.