title: The Drosophila FHOD1-like formin Knittrig acts through Rok to promote stress fiber formation and directed macrophage migration during the cellular immune response.
abstract: A tight spatiotemporal control of actin polymerization is important for many cellular processes that shape cells into a multicellular organism. The formation of unbranched F-actin is induced by several members of the formin family. Drosophila encodes six formin genes, representing six of the seven known mammalian subclasses. Knittrig, the Drosophila homolog of mammalian FHOD1, is specifically expressed in the developing central nervous system midline glia, the trachea, the wing and in macrophages. knittrig mutants exhibit mild tracheal defects but survive until late pupal stages and mainly die as pharate adult flies. knittrig mutant macrophages are smaller and show reduced cell spreading and cell migration in in vivo wounding experiments. Rescue experiments further demonstrate a cell-autonomous function of Knittrig in regulating actin dynamics and cell migration. Knittrig localizes at the rear of migrating macrophages in vivo, suggesting a cellular requirement of Knittrig in the retraction of the trailing edge. Supporting this notion, we found that Knittrig is a target of the Rho-dependent kinase Rok. Co-expression with Rok or expression of an activated form of Knittrig induces actin stress fibers in macrophages and in epithelial tissues. Thus, we propose a model in which Rok-induced phosphorylation of residues within the basic region mediates the activation of Knittrig in controlling macrophage migration.
authors.affiliation: Institute for Neurobiology, University of Münster, 48149 Münster, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Lammel
authors.forename: Meike
authors.initials: M
authors.lastname: Bechtold
authors.forename: Benjamin
authors.initials: B
authors.lastname: Risse
authors.forename: Dimitri
authors.initials: D
authors.lastname: Berh
authors.forename: Astrid
authors.initials: A
authors.lastname: Fleige
authors.forename: Ingrid
authors.initials: I
authors.lastname: Bunse
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Jiang
authors.forename: Christian
authors.initials: C
authors.lastname: Klämbt
authors.forename: Sven
authors.initials: S
authors.lastname: Bogdan
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000276:immunology / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D007111:Immunity, Cellular; D008264:Macrophages / Q000276:immunology / Q000502:physiology; D009154:Mutation; D022502:Stress Fibers / Q000378:metabolism; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D054460:rho-Associated Kinases
keywords: Cellular immune response; Drosophila; F-actin; Formin; Macrophages; Stress fiber; Tracheal development