Insight from the maximal activation of the signal transduction excitable network in Dictyostelium discoideum

Proc Natl Acad Sci U S A. 2018 Apr 17;115(16):E3722-E3730. doi: 10.1073/pnas.1710480115. Epub 2018 Mar 30.


Cell migration requires the coordination of an excitable signal transduction network involving Ras and PI3K pathways with cytoskeletal activity. We show that expressing activated Ras GTPase-family proteins in cells lacking PTEN or other mutations which increase cellular protrusiveness transforms cells into a persistently activated state. Leading- and trailing-edge markers were found exclusively at the cell perimeter and the cytosol, respectively, of the dramatically flattened cells. In addition, the lifetimes of dynamic actin puncta were increased where they overlapped with actin waves, suggesting a mechanism for the coupling between these two networks. All of these phenotypes could be reversed by inhibiting signal transduction. Strikingly, maintaining cells in this state of constant activation led to a form of cell death by catastrophic fragmentation. These findings provide insight into the feedback loops that control excitability of the signal transduction network, which drives migration.

Keywords: Dictyostelium; cell migration; chemotaxis; signal transduction; waves.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Actin Cytoskeleton / physiology
  • Actin Cytoskeleton / ultrastructure
  • Cell Adhesion
  • Cell Movement
  • Cell Shape
  • Chemotaxis
  • Dictyostelium / genetics
  • Dictyostelium / physiology*
  • Dictyostelium / ultrastructure
  • Enzyme Activation
  • Microscopy, Fluorescence
  • Microscopy, Phase-Contrast
  • Mutation, Missense
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / physiology
  • Phenotype
  • Protozoan Proteins / genetics
  • Protozoan Proteins / physiology*
  • Recombinant Proteins / metabolism
  • Signal Transduction / physiology*
  • rap1 GTP-Binding Proteins / genetics
  • rap1 GTP-Binding Proteins / physiology


  • Protozoan Proteins
  • Recombinant Proteins
  • PTEN Phosphohydrolase
  • rap1 GTP-Binding Proteins