title: WHAMY is a novel actin polymerase promoting myoblast fusion, macrophage cell motility and sensory organ development in Drosophila.
abstract: Wiskott-Aldrich syndrome proteins (WASPs) are nucleation-promoting factors (NPF) that differentially control the Arp2/3 complex. In Drosophila, three different family members, SCAR (also known as WAVE), WASP and WASH (also known as CG13176), have been analyzed so far. Here, we characterized WHAMY, the fourth Drosophila WASP family member. whamy originated from a wasp gene duplication and underwent a sub-neofunctionalization. Unlike WASP, we found that WHAMY specifically interacted with activated Rac1 through its two CRIB domains, which were sufficient for targeting WHAMY to lamellipodial and filopodial tips. Biochemical analyses showed that WHAMY promoted exceptionally fast actin filament elongation, although it did not activate the Arp2/3 complex. Loss- and gain-of-function studies revealed an important function of WHAMY in membrane protrusions and cell migration in macrophages. Genetic data further implied synergistic functions between WHAMY and WASP during morphogenesis. Double mutants were late-embryonic lethal and showed severe defects in myoblast fusion. Trans-heterozygous mutant animals showed strongly increased defects in sensory cell fate specification. Thus, WHAMY is a novel actin polymerase with an initial partitioning of ancestral WASP functions in development and subsequent acquisition of a new function in cell motility during evolution.
authors.affiliation: Institut für Neurobiologie, Universität Münster, Badestr. 9, Münster 48149, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Brinkmann
authors.affiliation: Institut für Biophysikalische Chemie, Medizinische Hochschule Hannover, Carl-Neuberg Strasse 1, Hannover 30625, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Winterhoff
authors.affiliation: Fachbereich Biologie, Entwicklungsbiologie, Philipps-Universität Marburg, Karl-von-Frisch Str. 8, Marburg 35043, Germany.
authors.forename: Susanne-Filiz
authors.initials: SF
authors.lastname: Önel
authors.affiliation: Center for Computational and Theoretical Biology, Campus Nord and Bioinformatik, Biozentrum, Am Hubland, Universität Würzburg, Würzburg 97074, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Schultz
authors.affiliation: Institut für Biophysikalische Chemie, Medizinische Hochschule Hannover, Carl-Neuberg Strasse 1, Hannover 30625, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Faix
authors.affiliation: Institut für Neurobiologie, Universität Münster, Badestr. 9, Münster 48149, Germany sbogdan@uni-muenster.de.
authors.forename: Sven
authors.initials: S
authors.lastname: Bogdan
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D004330:Drosophila / Q000378:metabolism* / Q000502:physiology; D029721:Drosophila Proteins / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism*; D009024:Morphogenesis / Q000502:physiology; D024510:Muscle Development / Q000502:physiology; D032446:Myoblasts / Q000378:metabolism*; D038081:Organogenesis / Q000502:physiology*; D051316:Wiskott-Aldrich Syndrome Protein / Q000378:metabolism
chemical_list: D000199:Actins; D029721:Drosophila Proteins; D008840:Microfilament Proteins; C573646:Whamy protein, Drosophila; D051316:Wiskott-Aldrich Syndrome Protein
keywords: Actin assembly; Cell migration; Cellular immune response; JMY; Macrophage; Myoblast fusion; Sensory organ development; WASP; WAVE; WHAMM