Cell polarization is a basic cell biological process necessary for the function of most cells. Classical examples of polarized cells include neurons, with specialized dendrites and axons respectively receiving and transmitting electrical signals, or epithelial cells with specialized surfaces contacting the inside and outside world. In fact, most, if not all cells, even unicellular organisms, are spatially organized in a polarized manner. While eukaryotic cells show a vast diversity of shapes and functions, basic concepts of cell polarization are remarkably conserved. The proposed project uses a simple unicellular model system, the fission yeast Schizosaccharomyces pombe, to study this important problem.
The unicellular yeast models have been instrumental in deciphering the mechanisms of cell polarization and establishing basic concepts: Cell polarity is generally initiated by a cell surface landmark, which marks the site towards which the cell orients. The landmark can be positioned either in response to intrinsic signals or in response to extracellular cues. In either case, the landmark then leads to the local activation of a signaling molecule, the small GTPase Cdc42. In turn, Cdc42 activates signaling pathways for cell polarization. One important question is how landmarks recruit Cdc42 for polarization.
The project has two broad aims. The first is to dissect how landmarks lead to the local activation of Cdc42 during vegetative growth. Fission yeast cells are rod-shaped, a shape that is maintained by directing growth exclusively to the extremities of the cell. Landmarks are deposited at these locations by the microtubule cytoskeleton. It is however not understood how these connect to Cdc42 and restrict it its local activation at cell extremities.
The second broad aim is to establish the fission yeast system as a robust model in which to study pheromone-dependent cell polarization. For sexual reproduction, cells of opposite mating type (sexes) secrete chemo-attractant molecules known as pheromones, which are recognized by potential mates. This induces polarized cell growth in the direction of the mating partner, which ultimately leads to cell fusion and production of highly resistant spores. This process is very poorly studied in fission yeast, which is otherwise an excellent cell biological model system. We will perform genetic screens to search for genes involved in this process. One particular aim will be to reveal how pheromones lead to local Cdc42 activation.
In summary, our work will provide novel insights into the initial steps of cell polarization. Since most components important for cell polarization are conserved from yeast to higher eukaryotes, the proposed research is likely to provide general conceptual advance valid beyond the yeast model.