Directional sensing in eukaryotic chemotaxis: A balanced inactivation model

Herbert Levine, David A. Kessler, Wouter Jan Rappel

Research output: Contribution to journalArticlepeer-review

128 Scopus citations

Abstract

Many eukaryotic cells, including Dictyostelium discoideum amoebae, fibroblasts, and neutrophils, are able to respond to chemoattractant gradients with high sensitivity. Recent studies have demonstrated that, after the introduction of a chemoattractant gradient, several chemotaxis pathway components exhibit a subcellular reorganization that cannot be described as a simple amplification of the external gradient. Instead, this reorganization has the characteristics of a switch, leading to a well defined front and back. Here, we propose a directional sensing mechanism in which two second messengers are produced at equal rates. The diffusion of one of them, coupled with an inactivation scheme, ensures a switch-like response to external gradients for a large range of gradient steepness and average concentration. Furthermore, our model is able to reverse the subcellular organization rapidly, and its response to multiple simultaneous chemoattractant sources is in good agreement with recent experimental results. Finally, we propose that the dynamics of a heterotrimeric G protein might allow for a specific biochemical realization of our model.

Original languageEnglish
Pages (from-to)9761-9766
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number26
DOIs
StatePublished - 27 Jun 2006

Keywords

  • Dynamics
  • Modeling

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