title: Distinct levels in Pom1 gradients limit Cdr2 activity and localization to time and position division.
abstract: Where and when cells divide are fundamental questions. In rod-shaped fission yeast cells, the DYRK-family kinase Pom1 is organized in concentration gradients from cell poles and controls cell division timing and positioning. Pom1 gradients restrict to mid-cell the SAD-like kinase Cdr2, which recruits Mid1/Anillin for medial division. Pom1 also delays mitotic commitment through Cdr2, which inhibits Wee1. Here, we describe quantitatively the distributions of cortical Pom1 and Cdr2. These reveal low profile overlap contrasting with previous whole-cell measurements and Cdr2 levels increase with cell elongation, raising the possibility that Pom1 regulates mitotic commitment by controlling Cdr2 medial levels. However, we show that distinct thresholds of Pom1 activity define the timing and positioning of division. Three conditions-a separation-of-function Pom1 allele, partial downregulation of Pom1 activity, and haploinsufficiency in diploid cells-yield cells that divide early, similar to pom1 deletion, but medially, like wild-type cells. In these cells, Cdr2 is localized correctly at mid-cell. Further, Cdr2 overexpression promotes precocious mitosis only in absence of Pom1. Thus, Pom1 inhibits Cdr2 for mitotic commitment independently of regulating its localization or cortical levels. Indeed, we show Pom1 restricts Cdr2 activity through phosphorylation of a C-terminal self-inhibitory tail. In summary, our results demonstrate that distinct levels in Pom1 gradients delineate a medial Cdr2 domain, for cell division placement, and control its activity, for mitotic commitment.
authors: Department of Fundamental Microbiology; University of Lausanne; Lausanne, Switzerland.
authors: Payal
authors: P
authors: Bhatia
authors: Department of Fundamental Microbiology; University of Lausanne; Lausanne, Switzerland.
authors: Olivier
authors: O
authors: Hachet
authors: Department of Medical Genetics; University of Lausanne; Lausanne, Switzerland; Swiss Institute of Bioinformatics; University of Lausanne; Lausanne, Switzerland.
authors: Micha
authors: M
authors: Hersch
authors: Institut Curie; CNRS UMR144; Paris, France; CNRS UMR144; Paris, France.
authors: Sergio A
authors: SA
authors: Rincon
authors: Department of Fundamental Microbiology; University of Lausanne; Lausanne, Switzerland.
authors: Martine
authors: M
authors: Berthelot-Grosjean
authors: Department of Medical Genetics; University of Lausanne; Lausanne, Switzerland; Swiss Institute of Bioinformatics; University of Lausanne; Lausanne, Switzerland.
authors: Sascha
authors: S
authors: Dalessi
authors: Department of Fundamental Microbiology; University of Lausanne; Lausanne, Switzerland.
authors: Laetitia
authors: L
authors: Basterra
authors: Department of Medical Genetics; University of Lausanne; Lausanne, Switzerland; Swiss Institute of Bioinformatics; University of Lausanne; Lausanne, Switzerland.
authors: Sven
authors: S
authors: Bergmann
authors: Institut Curie; CNRS UMR144; Paris, France; CNRS UMR144; Paris, France.
authors: Anne
authors: A
authors: Paoletti
authors: Department of Fundamental Microbiology; University of Lausanne; Lausanne, Switzerland.
authors: Sophie G
authors: SG
authors: Martin
mesh_terms: D002453:Cell Cycle; D002455:Cell Division; D048429:Cell Size; D008938:Mitosis; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D029702:Schizosaccharomyces pombe Proteins; D011494:Protein Kinases; C112212:Pom1 protein, S pombe; C542567:Cdr2 protein, S pombe; D017346:Protein Serine-Threonine Kinases
keywords: Pom1 DYRK kinase; Schizosaccharomyces pombe; cell cycle; cell division; cell growth; fission; gradient; yeast