Publication

Coupled Excitable Ras and F-actin activation mediate spontaneous pseudopod formation and directed cell movement

van Haastert, P. J. M., Keizer-Gunnink, I. & Kortholt, A. 1-Apr-2017 In : Molecular Biology of the Cell. 28, 7, p. 922-934 13 p.

Research output: Scientific - peer-reviewArticle

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  • Coupled excitable Ras and F-actin activation mediates spontaneous pseudopod formation and directed cell movement

    Final publisher's version, 7 MB, PDF-document

DOI

Many eukaryotic cells regulate their mobility by external cues. Genetic studies have identified >100 components that participate in chemotaxis, which hinders the identification of the conceptual framework of how cells sense and respond to shallow chemical gradients. The activation of Ras occurs during basal locomotion and is an essential connector between receptor and cytoskeleton during chemotaxis. Using a sensitive assay for activated Ras, we show here that activation of Ras and F-actin forms two excitable systems that are coupled through mutual positive feedback and memory. This coupled excitable system leads to short-lived patches of activated Ras and associated F-actin that precede the extension of protrusions. In buffer, excitability starts frequently with Ras activation in the back/side of the cell or with F-actin in the front of the cell. In a shallow gradient of chemoattractant, local Ras activation triggers full excitation of Ras and subsequently F-actin at the side of the cell facing the chemoattractant, leading to directed pseudopod extension and chemotaxis. A computational model shows that the coupled excitable Ras/F-actin system forms the driving heart for the ordered-stochastic extension of pseudopods in buffer and for efficient directional extension of pseudopods in chemotactic gradients.

Original languageEnglish
Pages (from-to)922-934
Number of pages13
JournalMolecular Biology of the Cell
Volume28
Issue number7
Early online date1-Feb-2017
StatePublished - 1-Apr-2017

    Keywords

  • DICTYOSTELIUM CHEMOTAXIS, CHEMOATTRACTANT GRADIENTS, EUKARYOTIC CHEMOTAXIS, SIGNALING PATHWAYS, SHALLOW GRADIENTS, AMEBOID CELLS, MIGRATION, DYNAMICS, ORIENTATION, PERSISTENCE

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