Regulation of cell adhesion, polarity and proliferation in mammalian epithelial celles by proteins of the discs large and crumbs group

Ziel

Epithelial tumours are characterized by a loss of their polarized cellular architecture, which is correlated with less adhesive and more migratory properties of the tumour cell. Genetic analysis in Drosophila melanogaster led to the identification of the bazo oka, crumbs and discs large group of genes implicated in the generation of cell polarity. In addition, the components of the discs large group, the tumour suppressor proteins Dlg/Lgl/Scrib are involved in the regulation of cell proliferation. However, the f unction of these genes in mammals is poorly understood.

The proposed project aims to understand how the proteins of the crumbs and discs large group regulate cell adhesion in mammalian epithelial cells and how they contribute to cell polarity. Moreover, the studies are anticipated to identify the important linkage between the regulation of cell polarity and cell proliferation. The main approaches and methods for the research project is a wound healing migration assay and siRNA experiments. By using these as says, we will look at the biochemistry and cell biology of the de novo assembly of epithelial cell junctions. In particular, we will focus on the identification of the network of protein interactions between components of the bazooka, crumbs and discs large group and how these protein complexes contribute to cell junction formation and cell polarity. Furthermore, the role of Rho-family GTPases such as Rho, Rad and Cdc42 in the formation of cell adhesion will be assessed.

Finally, the proteins Dig, Lgl and S crib are considered to have a potential function in the control of cell proliferation. We will dissect the molecular events by which these proteins link cell polarity and cell proliferation by using a combination of siRNA, microinjection and live-cell imaging techniques. The results of the proposed project will have important implications for the field of epithelial cell biology and embryonic development.

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UNIVERSITY COLLEGE LONDON

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Gower Street
LONDON
Vereinigtes Königreich

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