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

Marc Edwards, Huaqing Cai, Bedri Abubaker-Sharif, Yu Long, Thomas J. Lampert, Peter N. Devreotes

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)E3722-E3730
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number16
DOIs
StatePublished - Apr 17 2018

Keywords

  • Cell migration
  • Chemotaxis
  • Dictyostelium
  • Signal transduction
  • Waves

ASJC Scopus subject areas

  • General

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