title: tsunami, the Dictyostelium homolog of the Fused kinase, is required for polarization and chemotaxis.
abstract: In a forward genetic screen for chemotaxis mutants in Dictyostelium discoideum, we identified a loss-of-function mutation, designated tsunami, encoding a homolog of the Fused kinase. Cells lacking tsuA function could not effectively perform chemotaxis and were unable to become polarized or correctly orient pseudopods in chemotactic gradients. While tsuA(-) cells were able to couple receptor occupancy to phosphatidylinositol (3,4,5) trisphosphate (PIP3) production and actin polymerization, the PIP3 response was prolonged and basal F-actin levels were increased. Interestingly, TsuA localizes to the microtubule network and puncta mainly found at the cell periphery. Analysis of the gene uncovered a novel C-terminal domain that we designated the Tsunami Homology (TH) domain. Both the kinase domain and the TH domain are required to rescue the phenotypic defects of tsuA(-) cells. While kinase activity is not required for localization to microtubules, the TH domain is essential. Thus, localization of kinase activity to microtubules is critical for TsuA function. We propose that functions in association with the microtubule network may underlie the divergent roles of Fused kinase proteins in different organisms.
authors: Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors: Linnan
authors: L
authors: Tang
authors: Jonathan
authors: J
authors: Franca-Koh
authors: Yuan
authors: Y
authors: Xiong
authors: Mei-Yu
authors: MY
authors: Chen
authors: Yu
authors: Y
authors: Long
authors: Ross M
authors: RM
authors: Bickford
authors: David A
authors: DA
authors: Knecht
authors: Pablo A
authors: PA
authors: Iglesias
authors: Peter N
authors: PN
authors: Devreotes
mesh_terms: D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D016764:Cell Polarity; D002633:Chemotaxis / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism; D004023:Dictyostelium / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism*; D020869:Gene Expression Profiling; D008870:Microtubules / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D010716:Phosphatidylinositols / Q000378:metabolism; D021381:Protein Transport; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013347:Subcellular Fractions
chemical_list: D000199:Actins; D029721:Drosophila Proteins; D010716:Phosphatidylinositols; C118303:phosphoinositide-3,4,5-triphosphate; D000242:Cyclic AMP