title: Mathematical model of a cell size checkpoint.
abstract: How cells regulate their size from one generation to the next has remained an enigma for decades. Recently, a molecular mechanism that links cell size and cell cycle was proposed in fission yeast. This mechanism involves changes in the spatial cellular distribution of two proteins, Pom1 and Cdr2, as the cell grows. Pom1 inhibits Cdr2 while Cdr2 promotes the G2 → M transition. Cdr2 is localized in the middle cell region (midcell) whereas the concentration of Pom1 is highest at the cell tips and declines towards the midcell. In short cells, Pom1 efficiently inhibits Cdr2. However, as cells grow, the Pom1 concentration at midcell decreases such that Cdr2 becomes activated at some critical size. In this study, the chemistry of Pom1 and Cdr2 was modeled using a deterministic reaction-diffusion-convection system interacting with a deterministic model describing microtubule dynamics. Simulations mimicked experimental data from wild-type (WT) fission yeast growing at normal and reduced rates; they also mimicked the behavior of a Pom1 overexpression mutant and WT yeast exposed to a microtubule depolymerizing drug. A mechanism linking cell size and cell cycle, involving the downstream action of Cdr2 on Wee1 phosphorylation, is proposed.
authors.affiliation: Department of Chemistry, Texas A&M University, College Station, Texas, United States of America.
authors.forename: Marco
authors.initials: M
authors.lastname: Vilela
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Morgan
authors.forename: Paul A
authors.initials: PA
authors.lastname: Lindahl
mesh_terms: D000465:Algorithms; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000378:metabolism; D049108:Cell Enlargement; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D008870:Microtubules; D008954:Models, Biological; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012568:Schizosaccharomyces / Q000254:growth & development / Q000502:physiology; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D029702:Schizosaccharomyces pombe Proteins; D011494:Protein Kinases; C112212:Pom1 protein, S pombe; C068689:wee1 protein, S pombe; D011505:Protein-Tyrosine Kinases; C542567:Cdr2 protein, S pombe; D017346:Protein Serine-Threonine Kinases