SCAR/WAVE is activated at mitosis and drives myosin-independent cytokinesis.
Cell division requires the tight coordination of multiple cytoskeletal pathways. The best understood of these involves myosin-II-dependent constriction around the cell equator, but both Dictyostelium and mammalian cells also use a parallel, adhesion-dependent mechanism to generate furrows. We show that the actin nucleation factor SCAR/WAVE is strongly activated during Dictyostelium cytokinesis. This activation localises to large polar protrusions, driving separation of the daughter cells. This continues for 10 minutes after division before the daughter cells revert to normal random motility, indicating that this is a tightly regulated process. We demonstrate that SCAR activity is essential to drive myosin-II-independent cytokinesis, and stabilises the furrow, ensuring symmetrical division. SCAR is also responsible for the generation of MiDASes, mitosis-specific actin-rich adhesions. Loss of SCAR in both Dictyostelium and Drosophila leads to a similar mitotic phenotype, with severe mitotic blebbing, indicating conserved functionality. We also find that the microtubule end-binding protein EB1 is required to restrict SCAR localisation and direct migration. EB1-null cells also exhibit decreased adhesion during mitosis. Our data reveal a spindle-directed signalling pathway that regulates SCAR activity, migration and adhesion at mitosis.
King
Jason S
JS
Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow, G61 1BD, UK. j.king@beatson.gla.ac.uk
Veltman
Douwe M
DM
Georgiou
Marios
M
Baum
Buzz
B
Insall
Robert H
RH
D000818:Animals; D002465:Cell Movement / Q000502:physiology; D048749:Cytokinesis / Q000502:physiology*; D004023:Dictyostelium / Q000166:cytology / Q000502:physiology; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008938:Mitosis / Q000502:physiology*; D009218:Myosins / Q000378:metabolism*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D008941:Spindle Apparatus / Q000378:metabolism
C405804:EB1 microtubule binding proteins; D008869:Microtubule-Associated Proteins; D021122:Protein Subunits; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; C491975:SCAR protein, Dictyostelium; D009218:Myosins