title: Rho GTPases orient directional sensing in chemotaxis.
abstract: During chemotaxis, cells sense extracellular chemical gradients and position Ras GTPase activation and phosphatidylinositol (3,4,5)-triphosphate (PIP3) production toward chemoattractants. These two major signaling events are visualized by biosensors in a crescent-like zone at the plasma membrane. Here, we show that a Dictyostelium Rho GTPase, RacE, and a guanine nucleotide exchange factor, GxcT, stabilize the orientation of Ras activation and PIP3 production in response to chemoattractant gradients, and this regulation occurred independently of the actin cytoskeleton and cell polarity. Cells lacking RacE or GxcT fail to persistently direct Ras activation and PIP3 production toward chemoattractants, leading to lateral pseudopod extension and impaired chemotaxis. Constitutively active forms of RacE and human RhoA are located on the portion of the plasma membrane that faces lower concentrations of chemoattractants, opposite of PIP3 production. Mechanisms that control the localization of the constitutively active form of RacE require its effector domain, but not PIP3. Our findings reveal a critical role for Rho GTPases in positioning Ras activation and thereby establishing the accuracy of directional sensing.
authors.affiliation: Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Senoo
authors.forename: Hiromi
authors.initials: H
authors.lastname: Sesaki
authors.forename: Miho
authors.initials: M
authors.lastname: Iijima
mesh_terms: D015139:Blotting, Southern; D002630:Chemotactic Factors / Q000378:metabolism*; D002633:Chemotaxis / Q000502:physiology*; D055786:Gene Knockout Techniques; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D018613:Microscopy, Confocal; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D020744:rac GTP-Binding Proteins / Q000378:metabolism* / Q000502:physiology
chemical_list: D002630:Chemotactic Factors; D020662:Guanine Nucleotide Exchange Factors; D018129:Phosphatidylinositol Phosphates; C100414:RacE protein, Dictyostelium discoideum; C060974:phosphatidylinositol 3,4,5-triphosphate; D020744:rac GTP-Binding Proteins