title: Four key signaling pathways mediating chemotaxis in Dictyostelium discoideum.
abstract: Chemotaxis is the ability of cells to move in the direction of an external gradient of signaling molecules. Cells are guided by actin-filled protrusions in the front, whereas myosin filaments retract the rear of the cell. Previous work demonstrated that chemotaxis of unpolarized amoeboid Dictyostelium discoideum cells is mediated by two parallel pathways, phosphoinositide-3-kinase (PI3K) and phospholipase A2 (PLA2). Here, we show that polarized cells exhibit very good chemotaxis with inhibited PI3K and PLA2 activity. Using genetic screens, we demonstrate that this activity is mediated by a soluble guanylyl cyclase, providing two signals. The protein localizes to the leading edge where it interacts with actin filaments, whereas the cyclic guanosine monophosphate product induces myosin filaments in the rear of the cell. We conclude that chemotaxis is mediated by multiple signaling pathways regulating protrusions at the front and rear of the cell. Cells that express only rear activity are polarized but do not exhibit chemotaxis, whereas cells with only front signaling are unpolarized but undergo chemotaxis.
authors.affiliation: Department of Molecular Cell Biology, University of Groningen, 9751 NN Haren, Netherlands.
authors.forename: Douwe M
authors.initials: DM
authors.lastname: Veltman
authors.forename: Ineke
authors.initials: I
authors.lastname: Keizer-Gunnik
authors.forename: Peter J M
authors.initials: PJ
authors.lastname: Van Haastert
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D002465:Cell Movement / Q000502:physiology; D016764:Cell Polarity / Q000502:physiology; D048430:Cell Shape / Q000502:physiology; D022081:Cell Surface Extensions / Q000201:enzymology / Q000648:ultrastructure; D002633:Chemotaxis / Q000502:physiology*; D004023:Dictyostelium / Q000201:enzymology* / Q000648:ultrastructure; D006157:Guanosine Monophosphate / Q000378:metabolism; D006162:Guanylate Cyclase / Q000378:metabolism; D009218:Myosins / Q000378:metabolism / Q000648:ultrastructure; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D054467:Phospholipases A2 / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D000071756:Soluble Guanylyl Cyclase
chemical_list: D018160:Receptors, Cytoplasmic and Nuclear; D006157:Guanosine Monophosphate; D019869:Phosphatidylinositol 3-Kinases; D054467:Phospholipases A2; D009218:Myosins; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase