SCAR/WAVE and Arp2/3 are crucial for cytoskeletal remodeling at the site of myoblast fusion.
Myoblast fusion is crucial for formation and repair of skeletal muscle. Here we show that active remodeling of the actin cytoskeleton is essential for fusion in Drosophila. Using live imaging, we have identified a dynamic F-actin accumulation (actin focus) at the site of fusion. Dissolution of the actin focus directly precedes a fusion event. Whereas several known fusion components regulate these actin foci, others target additional behaviors required for fusion. Mutations in kette/Nap1, an actin polymerization regulator, lead to enlarged foci that do not dissolve, consistent with the observed block in fusion. Kette is required to positively regulate SCAR/WAVE, which in turn activates the Arp2/3 complex. Mutants in SCAR and Arp2/3 have a fusion block and foci phenotype, suggesting that Kette-SCAR-Arp2/3 participate in an actin polymerization event required for focus dissolution. Our data identify a new paradigm for understanding the mechanisms underlying fusion in myoblasts and other tissues.
Richardson
Brian E
BE
Program in Developmental Biology, Sloan Kettering Institute, New York, NY 10021, USA.
Beckett
Karen
K
Nowak
Scott J
SJ
Baylies
Mary K
MK
D051376:Actin-Related Protein 2-3 Complex / Q000235:genetics / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D003599:Cytoskeleton / Q000378:metabolism; D004330:Drosophila / Q000166:cytology / Q000196:embryology* / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D017344:Genes, Insect; D008561:Membrane Fusion / Q000235:genetics / Q000502:physiology; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D009154:Mutation; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism*; D010641:Phenotype; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000235:genetics / Q000378:metabolism*
D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; D029721:Drosophila Proteins; D008840:Microfilament Proteins; C449671:SCAR protein, Drosophila; D051300:Wiskott-Aldrich Syndrome Protein Family