Cell polarity is a common feature of many different cell types, ranging from single-cell organisms, to mammalian
epithelial cells and is defined as asymmetry in cell shape and protein distribution. The process of cell polarization
is fundamental not only for many cellular functions but also for embryonic development and tissue maintenance.
Most of our knowledge about the molecular mechanism controlling cell polarity has been gained from studies using
the model genetic systems Caenorhabditis elegans and Drosophila melanogaster. To date three distinct,
evolutionarily conserved protein complexes have been identified: Par-, Crumbs-, and Scrib-complex. The
components of these protein-complexes functionally and physically interact and act synergistically to control
numerous aspects of cell polarity, including the formation of cellular junctions, epithelial polarization, vesicle
trafficking, microtubule assembly, asymmetric cell division, and cell proliferation. However, despite this progress
our knowledge about the integration and molecular composition of these complexes during cell polarization is still
limited.
The aim of this study is to define novel binding partners of polarity proteins. Therefore, proteins such as Lgl1,
Lgl2, Scribble, or Dlg, will be immunoprecipitated from epithelial cells and the associated polypeptides will be
identified by the use of LC-tandem mass spectrometry (MS). We will be especially interested in proteins that are
implicated in vesicle transport/protein trafficking, the regulation of Rho, Rab and Arf family GTPases, control of
the cytoskeleton, and mitogenic signalling pathways. In subsequent studies we will employ a combination of
molecular biology, biochemistry, proteomics and bioinformatics to investigate the localization of the identified
binding partners and their influence on the protein complexes that ultimately regulate cell polarity.
The results of this study will extend our knowledge about the molecular mechanisms controlling the different facets
of cell polarization in epithelial cells. Furthermore, as the loss of polarity control in epithelial cells is an important
factor in the progression of carcinomas, our study will also contribute to our understanding of how these polarity
complexes are coupled to the control of cell proliferation and are involved in tumor suppression.