Abstract
Cell polarization is an important process involved in cell development, migration, and the onset of disease. Cdc42 is a Rho-family GTPase that controls cell polarization from yeast to human cells. In the fission yeast Schizosaccharomyces pombe, Cdc42-GTP oscillates between cell tips to promote polarized growth under normal growth conditions. However, when exposed to environmental stressors, such as nitrogen starvation or heat, active Cdc42 adopts an “exploratory” pattern of distribution along the cell membrane. This pattern also occurs when the conserved NDR kinase Orb6 is downregulated. Further, exposure to nitrogen starvation leads to a decrease in Orb6 activity, suggesting a link between stress signaling and Orb6 regulation. Here, I describe the molecular mechanism behind the emergence of exploratory Cdc42 dynamics and identify a substrate of Orb6 kinase, the Cdc42 GAP Rga3. Additionally, I show that MAP kinase Sty1, known for linking stress signals to the Cdc42 polarity module, negatively regulates Orb6 kinase during nitrogen starvation or heat stress. Consistent with the role of Orb6 in modulating stress response, Orb6 downregulation promotes heat stress resilience. These findings reveal a mechanism controlling cell morphology during stress, with important implications for cell survival. Due to the highly conserved nature of both NDR and MAP kinases, these findings will likely translate to higher eukaryotes, such as humans.