Grant: Operating Grant

Epithelial cells such as those found in intestine or skin are divided into distinct domains. One of these domains contains cell adhesion proteins necessary to ensure a tight seal between cells. This tight seal forms a permeability barrier that stops the flow of liquid and pathogens between cells and ensures that the two sides of the cell are isolated. This is an essential part of the formation of intestine, skin, stomach, kidney etc. It is clear how the permeability barrier forms at the boundary between two cells but less is known about how the corners of cells create the permeability barrier. At the corners, three cells come together and the pore between them is blocked by a unique structure called the tricellular junction. To study how this important junction forms, we study the Gliotactin protein, which is uniquely located at the contact point between three neighbouring cells in Drosophila (fruit fly). In fruit flies, like in humans, the tricellular junction is essential to create a permeability barrier at the corners of cells. Gliotactin is a membrane protein that localizes to the tricellular junction and is necessary for its formation. If we understand how Gliotactin is controlled we can then understand how the tricellular junction is created and how it functions. Gliotactin is highly conserved with a family of protein in humans called Neuroligins. The function of these proteins in the formation of cell junctions/barriers outside the nervous system has never been studied. Therefore we can take advantage of the ease of the genetics and cell biology capable in Drosophila to understand the function of this family of proteins in epithelial cells in all animals.