Regulation of Polarity by Microtubules

Cell polarity is essential for cellular functions, growth, development, and formation of multicellular organisms. Cell polarization is often regulated during the cell division cycle. For instance, many cell types lose polarity and round up during mitosis, and then reestablish polarity after division. The fission yeast Schizosaccharomyces pombe is a model system for studying cell polarization. These unicellular rod-shaped cells grow by extension from their tips, and then stop growth during mitosis. Upon cytokinesis, they initiate growth from the old cell end and later in interphase, initiate growth at the second cell end in a process known as "new end take off" or NETO. NETO is regulated by polarity proteins tea1p and tea4p which are deposited by microtubules at the cell tips. How these proteins regulate cell polarity is not yet well understood. These polarity proteins are thought to function in recruiting other proteins, which leads to localized actin polymerization, membrane trafficking and cell wall assembly, leading ultimately to polarized cell growth at the cell tip. In this thesis, I report the characterization of a new polarity protein tea5p in fission yeast. I identified tea5p in a screen for new NETO mutants. Tea5p is a new component of the tea-protein polarity pathway. It resides at cell tips in complexes with the other polarity proteins tea1p and tea3p, and functions downstream of tea1p. Genetic interactions suggest that tea5p regulates polarized growth by regulating the small GTPase cdc42p and its activator gef1p. Tea5p is a pseudokinase that binds to the plasma membrane with its N terminus, and requires its kinase like domain for function. Together my results begin to establish a pathway that links microtubules to activation of cdc42p for regulation for polarized growth in S. pombe.