title: PKA antagonizes CLASP-dependent microtubule stabilization to re-localize Pom1 and buffer cell size upon glucose limitation.
abstract: Cells couple growth with division and regulate size in response to nutrient availability. In rod-shaped fission yeast, cell-size control occurs at mitotic commitment. An important regulator is the DYRK-family kinase Pom1, which forms gradients from cell poles and inhibits the mitotic activator Cdr2, itself localized at the medial cortex. Where and when Pom1 modulates Cdr2 activity is unclear as Pom1 medial cortical levels remain constant during cell elongation. Here we show that Pom1 re-localizes to cell sides upon environmental glucose limitation, where it strongly delays mitosis. This re-localization is caused by severe microtubule destabilization upon glucose starvation, with microtubules undergoing catastrophe and depositing the Pom1 gradient nucleator Tea4 at cell sides. Microtubule destabilization requires PKA/Pka1 activity, which negatively regulates the microtubule rescue factor CLASP/Cls1/Peg1, reducing CLASP's ability to stabilize microtubules. Thus, PKA signalling tunes CLASP's activity to promote Pom1 cell side localization and buffer cell size upon glucose starvation.
authors.affiliation: Department of Fundamental Microbiology, University of Lausanne, Biophore Building, CH-1015 Lausanne, Switzerland.
authors.forename: Manasi
authors.initials: M
authors.lastname: Kelkar
authors.affiliation: Department of Fundamental Microbiology, University of Lausanne, Biophore Building, CH-1015 Lausanne, Switzerland.
authors.forename: Sophie G
authors.identifier: http://orcid.org/0000-0002-5317-2557
authors.initials: SG
authors.lastname: Martin
mesh_terms: D015153:Blotting, Western; D016764:Cell Polarity; D048429:Cell Size; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism*; D008938:Mitosis; D009687:Nuclear Proteins / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012568:Schizosaccharomyces / Q000166:cytology / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*
chemical_list: D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; C513960:Peg1 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins; C501888:Tea4 protein, S pombe; D011494:Protein Kinases; C112212:Pom1 protein, S pombe; C542567:Cdr2 protein, S pombe; D017346:Protein Serine-Threonine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D005947:Glucose