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

Hiroshi Senoo, Huaqing Caia, Yu Wang, Hiromi Sesaki, Miho Iijima

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1596-1605
Number of pages10
JournalMolecular Biology of the Cell
Volume27
Issue number10
DOIs
Publication statusPublished - May 15 2016

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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