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PMID: 20530573 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

SCAR/WAVE is activated at mitosis and drives myosin-independent cytokinesis.

Journal of cell science ·Vol. 123 ·No. Pt 13 ·2010-07-01 ·Pages 2246-55

King JS, Veltman DM, Georgiou M, Baum B, Insall RH

Abstract

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.

MeSH Terms
Animals Cell Movement/physiology Cytokinesis/physiology Dictyostelium/cytology,physiology Microtubule-Associated Proteins/genetics,metabolism Mitosis/physiology Myosins/metabolism Protein Subunits/genetics,metabolism Protozoan Proteins/genetics,metabolism Recombinant Fusion Proteins/genetics,metabolism Signal Transduction/physiology Spindle Apparatus/metabolism
Chemicals
EB1 microtubule binding proteins Microtubule-Associated Proteins Protein Subunits Protozoan Proteins Recombinant Fusion Proteins SCAR protein, Dictyostelium Myosins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
King Jason S
Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow, G61 1BD, UK. j.king@beatson.gla.ac.uk
Veltman Douwe M
Georgiou Marios
Baum Buzz
Insall Robert H
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Article Info
Journal
Journal of cell science
Abbr.
J Cell Sci
ISSN
1477-9137
DOI
10.1242/jcs.063735
Email
j.king@beatson.gla.ac.uk
Published
2010-07-01
Epub
2010-00-08
Pages
2246-55
Language
English
Region
England
NLM ID
0052457
PMCID
PMC2886745
Subset
IM
Grants
Cancer Research UK · 9786 · United Kingdom
Medical Research Council · G0600249 · United Kingdom
Medical Research Council · G117/537 · United Kingdom
External Links
PubMed source DOI: 10.1242/jcs.063735 PMC Full Text View journal details
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