Evolutionarily conserved coupling of adaptive and excitable networks mediates eukaryotic chemotaxis

Nat Commun. 2014 Oct 27;5:5175. doi: 10.1038/ncomms6175.


Numerous models explain how cells sense and migrate towards shallow chemoattractant gradients. Studies show that an excitable signal transduction network acts as a pacemaker that controls the cytoskeleton to drive motility. Here we show that this network is required to link stimuli to actin polymerization and chemotactic motility and we distinguish the various models of chemotaxis. First, signalling activity is suppressed towards the low side in a gradient or following removal of uniform chemoattractant. Second, signalling activities display a rapid shut off and a slower adaptation during which responsiveness to subsequent test stimuli decline. Simulations of various models indicate that these properties require coupled adaptive and excitable networks. Adaptation involves a G-protein-independent inhibitor, as stimulation of cells lacking G-protein function suppresses basal activities. The salient features of the coupled networks were observed for different chemoattractants in Dictyostelium and in human neutrophils, suggesting an evolutionarily conserved mechanism for eukaryotic chemotaxis.

Publication types

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

MeSH terms

  • Adaptation, Physiological* / drug effects
  • Biological Evolution*
  • Cells, Immobilized / cytology
  • Cells, Immobilized / drug effects
  • Chemotactic Factors / pharmacology
  • Chemotaxis* / drug effects
  • Dictyostelium / cytology*
  • Dictyostelium / drug effects
  • Eukaryotic Cells / cytology*
  • Eukaryotic Cells / drug effects
  • GTP-Binding Proteins / metabolism
  • Humans
  • Kinetics
  • Models, Biological
  • Neutrophils / cytology*
  • Neutrophils / drug effects
  • Signal Transduction* / drug effects


  • Chemotactic Factors
  • GTP-Binding Proteins