title: The novel RacE-binding protein GflB sharpens Ras activity at the leading edge of migrating cells.
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.
authors.affiliation: Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Senoo
authors.affiliation: Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205 State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Huaqing
authors.initials: H
authors.lastname: Cai
authors.affiliation: Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Sesaki
authors.affiliation: Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205 miijima@jhmi.edu.
authors.forename: Miho
authors.initials: M
authors.lastname: Iijima
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology; D002633:Chemotaxis / Q000502:physiology; D000242:Cyclic AMP; D004023:Dictyostelium / Q000235:genetics* / Q000378:metabolism*; D020690:GTPase-Activating Proteins; D011485:Protein Binding; D000072417:Protein Domains; D015800:Protozoan Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D018631:ras Proteins / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D020690:GTPase-Activating Proteins; D015800:Protozoan Proteins; C085379:rho GTPase-activating protein; D000242:Cyclic AMP; D018631:ras Proteins; D020741:rho GTP-Binding Proteins