title: Dock mediates Scar- and WASp-dependent actin polymerization through interaction with cell adhesion molecules in founder cells and fusion-competent myoblasts.
abstract: The formation of the larval body wall musculature of Drosophila depends on the asymmetric fusion of two myoblast types, founder cells (FCs) and fusion-competent myoblasts (FCMs). Recent studies have established an essential function of Arp2/3-based actin polymerization during myoblast fusion, formation of a dense actin focus at the site of fusion in FCMs, and a thin sheath of actin in FCs and/or growing muscles. The formation of these actin structures depends on recognition and adhesion of myoblasts that is mediated by cell surface receptors of the immunoglobulin superfamily. However, the connection of the cell surface receptors with Arp2/3-based actin polymerization is poorly understood. To date only the SH2-SH3 adaptor protein Crk has been suggested to link cell adhesion with Arp2/3-based actin polymerization in FCMs. Here, we propose that the SH2-SH3 adaptor protein Dock, like Crk, links cell adhesion with actin polymerization. We show that Dock is expressed in FCs and FCMs and colocalizes with the cell adhesion proteins Sns and Duf at cell-cell contact points. Biochemical data in this study indicate that different domains of Dock are involved in binding the cell adhesion molecules Duf, Rst, Sns and Hbs. We emphasize the importance of these interactions by quantifying the enhanced myoblast fusion defects in duf dock, sns dock and hbs dock double mutants. Additionally, we show that Dock interacts biochemically and genetically with Drosophila Scar, Vrp1 and WASp. Based on these data, we propose that Dock links cell adhesion in FCs and FCMs with either Scar- or Vrp1-WASp-dependent Arp2/3 activation.
authors.affiliation: Fachbereich Biologie, Entwicklungsbiologie, Philipps-Universität Marburg, Karl-von-Frisch Str. 8, D-35043 Marburg, Germany.
authors.forename: Balasankara Reddy
authors.initials: BR
authors.lastname: Kaipa
authors.forename: Huanjie
authors.initials: H
authors.lastname: Shao
authors.forename: Gritt
authors.initials: G
authors.lastname: Schäfer
authors.forename: Tatjana
authors.initials: T
authors.lastname: Trinkewitz
authors.forename: Verena
authors.initials: V
authors.lastname: Groth
authors.forename: Jianqi
authors.initials: J
authors.lastname: Liu
authors.forename: Lothar
authors.initials: L
authors.lastname: Beck
authors.forename: Sven
authors.initials: S
authors.lastname: Bogdan
authors.forename: Susan M
authors.initials: SM
authors.lastname: Abmayr
authors.forename: Susanne-Filiz
authors.initials: SF
authors.lastname: Önel
mesh_terms: D000199:Actins / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D024510:Muscle Development / Q000235:genetics / Q000502:physiology; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology* / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D051316:Wiskott-Aldrich Syndrome Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D015815:Cell Adhesion Molecules; D029721:Drosophila Proteins; D007136:Immunoglobulins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; C449671:SCAR protein, Drosophila; C410904:SNS protein, Drosophila; C553415:Vrp1 protein, Drosophila; C477859:WASp protein, Drosophila; D051316:Wiskott-Aldrich Syndrome Protein; C099753:dock protein, Drosophila; C442230:hbs protein, Drosophila; C413082:kirre protein, Drosophila