Robust cell size checkpoint from spatiotemporal positive feedback loop in fission yeast

Biomed Res Int. 2013:2013:910941. doi: 10.1155/2013/910941. Epub 2013 Jul 11.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle / genetics
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Cell Polarity / genetics*
  • Cell Proliferation
  • Cell Size
  • Mitosis / genetics
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Phosphoprotein Phosphatases / genetics*
  • Phosphoprotein Phosphatases / metabolism
  • Protein Kinases / genetics*
  • Protein-Tyrosine Kinases / genetics*
  • Protein-Tyrosine Kinases / metabolism
  • Schizosaccharomyces / genetics
  • Schizosaccharomyces / metabolism
  • Schizosaccharomyces pombe Proteins / genetics*
  • Schizosaccharomyces pombe Proteins / metabolism

Substances

  • Cell Cycle Proteins
  • Nuclear Proteins
  • Schizosaccharomyces pombe Proteins
  • Protein Kinases
  • Pom1 protein, S pombe
  • wee1 protein, S pombe
  • Protein-Tyrosine Kinases
  • Cdc25 protein, S pombe
  • Phosphoprotein Phosphatases