title: Competition between Blown fuse and WASP for WIP binding regulates the dynamics of WASP-dependent actin polymerization in vivo.
abstract: Dynamic rearrangements of the actin cytoskeleton play a key role in numerous cellular processes. In Drosophila, fusion between a muscle founder cell and a fusion competent myoblast (FCM) is mediated by an invasive, F-actin-enriched podosome-like structure (PLS). Here, we show that the dynamics of the PLS is controlled by Blown fuse (Blow), a cytoplasmic protein required for myoblast fusion but whose molecular function has been elusive. We demonstrate that Blow is an FCM-specific protein that colocalizes with WASP, WIP/Solitary, and the actin focus within the PLS. Biochemically, Blow modulates the stability of the WASP-WIP complex by competing with WASP for WIP binding, leading to a rapid exchange of WASP, WIP and G-actin within the PLS, which, in turn, actively invades the adjacent founder cell to promote fusion pore formation. These studies identify a regulatory protein that modulates the actin cytoskeletal dynamics by controlling the stability of the WASP-WIP complex.
authors.affiliation: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Jin
authors.forename: Rui
authors.initials: R
authors.lastname: Duan
authors.forename: Fengbao
authors.initials: F
authors.lastname: Luo
authors.forename: Guofeng
authors.initials: G
authors.lastname: Zhang
authors.forename: Sabrina N
authors.initials: SN
authors.lastname: Hong
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Chen
mesh_terms: D000199:Actins / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D002478:Cells, Cultured; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism*; D005260:Female; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism*; D051316:Wiskott-Aldrich Syndrome Protein / Q000378:metabolism*
chemical_list: D000199:Actins; D029721:Drosophila Proteins; D009124:Muscle Proteins; C477859:WASp protein, Drosophila; D051316:Wiskott-Aldrich Syndrome Protein; C105423:blow protein, Drosophila