title: The coordination of cell growth during fission yeast mating requires Ras1-GTP hydrolysis.
abstract: The spatial and temporal control of polarity is fundamental to the survival of all organisms. Cells define their polarity using highly conserved mechanisms that frequently rely upon the action of small GTPases, such as Ras and Cdc42. Schizosaccharomyces pombe is an ideal system with which to study the control of cell polarity since it grows from defined tips using Cdc42-mediated actin remodeling. Here we have investigated the importance of Ras1-GTPase activity for the coordination of polarized cell growth during fission yeast mating. Following pheromone stimulation, Ras1 regulates both a MAPK cascade and the activity of Cdc42 to enable uni-directional cell growth towards a potential mating partner. Like all GTPases, when bound to GTP, Ras1 adopts an active conformation returning to an inactive state upon GTP-hydrolysis, a process accelerated through interaction with negative regulators such as GAPs. Here we show that, at low levels of pheromone stimulation, loss of negative regulation of Ras1 increases signal transduction via the MAPK cascade. However, at the higher concentrations observed during mating, hyperactive Ras1 mutations promote cell death. We demonstrate that these cells die due to their failure to coordinate active Cdc42 into a single growth zone resulting in disorganized actin deposition and unsustainable elongation from multiple tips. These results provide a striking demonstration that the deactivation stage of Ras signaling is fundamentally important in modulating cell polarity.
authors.affiliation: Division of Biomedical Cell Biology, Warwick Medical School, University of Warwick, Coventry, United Kingdom.
authors.forename: Cathryn
authors.initials: C
authors.lastname: Weston
authors.forename: Michael
authors.initials: M
authors.lastname: Bond
authors.forename: Wayne
authors.initials: W
authors.lastname: Croft
authors.forename: Graham
authors.initials: G
authors.lastname: Ladds
mesh_terms: D000199:Actins / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism*; D006868:Hydrolysis; D010675:Pheromones / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D012568:Schizosaccharomyces / Q000502:physiology*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D000199:Actins; D010675:Pheromones; D029702:Schizosaccharomyces pombe Proteins; D006160:Guanosine Triphosphate; C492657:Ras1 protein, S pombe; D020764:cdc42 GTP-Binding Protein; D018631:ras Proteins