title: Robust cell size checkpoint from spatiotemporal positive feedback loop in fission yeast.
abstract: Cells must maintain appropriate cell size during proliferation. Size control may be regulated by a size checkpoint that couples cell size to cell division. Biological experimental data suggests that the cell size is coupled to the cell cycle in two ways: the rates of protein synthesis and the cell polarity protein kinase Pom1 provide spatial information that is used to regulate mitosis inhibitor Wee1. Here a mathematical model involving these spatiotemporal regulations was developed and used to explore the mechanisms underlying the size checkpoint in fission yeast. Bifurcation analysis shows that when the spatiotemporal regulation is coupled to the positive feedback loops (active Cdc2 promotes its activator, Cdc25, and suppress its inhibitor, Wee1), the mitosis-promoting factor (MPF) exhibits a bistable steady-state relationship with the cell size. The switch-like response from the positive feedback loops naturally generates the cell size checkpoint. Further analysis indicated that the spatial regulation provided by Pom1 enhances the robustness of the size checkpoint in fission yeast. This was consistent with experimental data.
authors: School of Mathematical Sciences, Soochow University, Suzhou 215006, China.
authors: Jie
authors: J
authors: Yan
authors: Xin
authors: X
authors: Ni
authors: Ling
authors: L
authors: Yang
mesh_terms: D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D016764:Cell Polarity / Q000235:genetics*; D049109:Cell Proliferation; D048429:Cell Size; D008938:Mitosis / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000235:genetics* / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics* / 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; C570820:Cdc25 protein, S pombe; D010749:Phosphoprotein Phosphatases
references: J Cell Sci. 1996 Dec;109 ( Pt 12):2947-57
references: 9013342
references: Nat Cell Biol. 2004 Sep;6(9):899-905
references: 15322555
references: Cell. 2005 Aug 26;122(4):565-78
references: 16122424
references: Science. 2008 Jul 4;321(5885):126-9
references: 18599789
references: Biophys Chem. 2001 Aug 30;92(1-2):1-15
references: 11527575
references: Exp Cell Res. 1977 Jul;107(2):377-86
references: 872891
references: Biophys Chem. 1998 May 5;72(1-2):185-200
references: 9652094
references: Mol Biol Cell. 2002 Jan;13(1):52-70
references: 11809822
references: Brief Funct Genomic Proteomic. 2004 Feb;2(4):298-307
references: 15163365
references: Biol Cell. 1998 Nov;90(8):537-48
references: 10068998
references: PLoS Comput Biol. 2010 Dec 16;6(12):e1001036
references: 21187911
references: J Cell Sci. 1977 Apr;24:51-67
references: 893551
references: Exp Cell Res. 1977 Jul;107(2):365-75
references: 872890
references: Proc Natl Acad Sci U S A. 2000 Jul 5;97(14):7865-70
references: 10884416
references: Science. 1996 Dec 6;274(5293):1646-52
references: 8939845
references: Nature. 2009 Jun 11;459(7248):852-6
references: 19474792
references: Chaos. 2001 Mar;11(1):277-286
references: 12779461
references: Biophys J. 2003 Dec;85(6):3600-11
references: 14645053
references: Exp Neurol. 1999 Apr;156(2):407-17
references: 10328945
references: J Cell Sci. 1993 Dec;106 ( Pt 4):1153-68
references: 8126097
references: J Exp Zool. 2000 Jul 1;287(2):128-44
references: 10900432
references: Mol Biol Cell. 2001 Dec;12(12):3892-903
references: 11739788
references: J Theor Biol. 2006 Jul 7;241(1):120-33
references: 16387327
references: Nature. 2009 Jun 11;459(7248):857-60
references: 19474789
references: J Theor Biol. 2009 Feb 21;256(4):485-92
references: 19056400
references: Curr Opin Cell Biol. 2002 Apr;14(2):140-8
references: 11891111
references: J Cell Sci. 2004 Aug 15;117(Pt 18):4199-207
references: 15280433