WIP/WASp-based actin-polymerization machinery is essential for myoblast fusion in Drosophila.
Formation of syncytial muscle fibers involves repeated rounds of cell fusion between growing myotubes and neighboring myoblasts. We have established that Wsp, the Drosophila homolog of the WASp family of microfilament nucleation-promoting factors, is an essential facilitator of myoblast fusion in Drosophila embryos. D-WIP, a homolog of the conserved Verprolin/WASp Interacting Protein family of WASp-binding proteins, performs a key mediating role in this context. D-WIP, which is expressed specifically in myoblasts, associates with both the WASp-Arp2/3 system and with the myoblast adhesion molecules Dumbfounded and Sticks and Stones, thereby recruiting the actin-polymerization machinery to sites of myoblast attachment and fusion. Our analysis demonstrates that this recruitment is normally required late in the fusion process, for enlargement of nascent fusion pores and breakdown of the apposed cell membranes. These observations identify cellular and developmental roles for the WASp-Arp2/3 pathway, and provide a link between force-generating actin polymerization and cell fusion.
Massarwa
R'ada
R
Department of Molecular Genetics, Weizmann Institute of Science, 76100 Rehovot, Israel.
Carmon
Shari
S
Shilo
Ben-Zion
BZ
Schejter
Eyal D
ED
D000199:Actins / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D002459:Cell Fusion; D002460:Cell Line; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D004625:Embryo, Nonmammalian; D007136:Immunoglobulins / Q000378:metabolism; D008954:Models, Biological; D024510:Muscle Development; D009132:Muscles / Q000196:embryology / Q000378:metabolism; D032446:Myoblasts / Q000378:metabolism / Q000502:physiology*; D051316:Wiskott-Aldrich Syndrome Protein / Q000235:genetics / Q000378:metabolism*
D000199:Actins; D029721:Drosophila Proteins; D007136:Immunoglobulins; C410904:SNS protein, Drosophila; C477859:WASp protein, Drosophila; D051316:Wiskott-Aldrich Syndrome Protein