title: Remodeling of the Fission Yeast Cdc42 Cell-Polarity Module via the Sty1 p38 Stress-Activated Protein Kinase Pathway.
abstract: The Rho family GTPase Cdc42 is a key regulator of eukaryotic cellular organization and cell polarity [1]. In the fission yeast Schizosaccharomyces pombe, active Cdc42 and associated effectors and regulators (the "Cdc42 polarity module") coordinate polarized growth at cell tips by controlling the actin cytoskeleton and exocytosis [2-4]. Localization of the Cdc42 polarity module to cell tips is thus critical for its function. Here we show that the fission yeast stress-activated protein kinase Sty1, a homolog of mammalian p38 MAP kinase, regulates localization of the Cdc42 polarity module. In wild-type cells, treatment with latrunculin A, a drug that leads to actin depolymerization, induces dispersal of the Cdc42 module from cell tips and cessation of polarized growth [5, 6]. We show that latrunculin A treatment also activates the Sty1 MAP kinase pathway and, strikingly, we find that loss of Sty1 MAP kinase signaling prevents latrunculin A-induced dispersal of the Cdc42 module, allowing polarized growth even in complete absence of the actin cytoskeleton. Regulation of the Cdc42 module by Sty1 is independent of Sty1's role in stress-induced gene expression. We also describe a system for activation of Sty1 kinase "on demand" in the absence of any external stress, and use this to show that Sty1 activation alone is sufficient to disperse the Cdc42 module from cell tips in otherwise unperturbed cells. During nitrogen-starvation-induced quiescence, inhibition of Sty1 converts non-growing, depolarized cells into growing, polarized cells. Our results place MAP kinase Sty1 as an important physiological regulator of the Cdc42 polarity module.
authors.affiliation: Wellcome Trust Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Michael Swann Building, Max Born Crescent, Edinburgh EH9 3BF, UK.
authors.forename: Delyan R
authors.initials: DR
authors.lastname: Mutavchiev
authors.affiliation: SynthSys (Centre for Synthetic and Systems Biology), School of Biological Sciences, University of Edinburgh, C.H. Waddington Building, Max Born Crescent, Edinburgh EH9 3BF, UK.
authors.forename: Marcin
authors.initials: M
authors.lastname: Leda
authors.affiliation: Wellcome Trust Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Michael Swann Building, Max Born Crescent, Edinburgh EH9 3BF, UK. Electronic address: ken.sawin@ed.ac.uk.
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Sawin
mesh_terms: D016764:Cell Polarity; D015966:Gene Expression Regulation, Fungal; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics / Q000502:physiology*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D029702:Schizosaccharomyces pombe Proteins; D020928:Mitogen-Activated Protein Kinases; C095409:sty1 protein, S pombe
keywords: Cdc42; MAP kinase; Schizosaccharomyces pombe; Sty1; actin; cell polarity; fission yeast; latrunculin; stress; yeast