The novel RacE-binding protein GflB sharpens Ras activity at the leading edge of migrating cells

Mol Biol Cell. 2016 May 15;27(10):1596-605. doi: 10.1091/mbc.E15-11-0796. Epub 2016 Mar 23.


Directional sensing, a process in which cells convert an external chemical gradient into internal signaling events, is essential in chemotaxis. We previously showed that a Rho GTPase, RacE, regulates gradient sensing in Dictyostelium cells. Here, using affinity purification and mass spectrometry, we identify a novel RacE-binding protein, GflB, which contains a Ras GEF domain and a Rho GAP domain. Using biochemical and gene knockout approaches, we show that GflB balances the activation of Ras and Rho GTPases, which enables cells to precisely orient signaling events toward higher concentrations of chemoattractants. Furthermore, we find that GflB is located at the leading edge of migrating cells, and this localization is regulated by the actin cytoskeleton and phosphatidylserine. Our findings provide a new molecular mechanism that connects directional sensing and morphological polarization.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Carrier Proteins / metabolism
  • Cell Movement / physiology
  • Chemotaxis / physiology
  • Cyclic AMP
  • Dictyostelium / genetics*
  • Dictyostelium / metabolism*
  • GTPase-Activating Proteins
  • Protein Binding
  • Protein Domains
  • Protozoan Proteins / metabolism
  • Signal Transduction / physiology
  • ras Proteins / metabolism
  • rho GTP-Binding Proteins / metabolism*


  • Carrier Proteins
  • GTPase-Activating Proteins
  • Protozoan Proteins
  • rho GTPase-activating protein
  • Cyclic AMP
  • ras Proteins
  • rho GTP-Binding Proteins