PUBLICATION
Inactivating negative regulators of cortical branched actin enhances persistence of single cell migration
- Authors
- Fokin, A.I., Boutillon, A., James, J., Courtois, L., Vacher, S., Simanov, G., Wang, Y., Polesskaya, A., Bièche, I., David, N.B., Gautreau, A.M.
- ID
- ZDB-PUB-231207-16
- Date
- 2023
- Source
- Journal of Cell Science 137(1): (Journal)
- Registered Authors
- David, Nicholas
- Keywords
- Arp2/3, Branched actin, Cell migration, Migration persistence, Vimentin
- MeSH Terms
-
- Actin-Related Protein 2-3 Complex/genetics
- Actin-Related Protein 2-3 Complex/metabolism
- Actins*/metabolism
- Animals
- Carrier Proteins/metabolism
- Cell Movement/physiology
- Humans
- Vimentin/genetics
- Vimentin/metabolism
- Zebrafish*/metabolism
- PubMed
- 38059420 Full text @ J. Cell Sci.
Citation
Fokin, A.I., Boutillon, A., James, J., Courtois, L., Vacher, S., Simanov, G., Wang, Y., Polesskaya, A., Bièche, I., David, N.B., Gautreau, A.M. (2023) Inactivating negative regulators of cortical branched actin enhances persistence of single cell migration. Journal of Cell Science. 137(1):.
Abstract
The Rac1-WAVE-Arp2/3 pathway pushes the plasma membrane by polymerizing branched actin, thereby powering membrane protrusions that mediate cell migration. Here, using knock-down (KD) or knock-out (KO), we combine the inactivation of the Arp2/3 inhibitory protein Arpin, the Arp2/3 subunit ARPC1A and the WAVE complex subunit, CYFIP2, that all enhance the polymerization of cortical branched actin (CBA). Inactivation of the 3 CBA negative regulators increases migration persistence of human breast MCF10A cells, and of endodermal cells in the zebrafish embryo, significantly more than any single or double inactivation. In the triple KO, but not triple KD cells, the "super-migrator" phenotype was associated with a heterogenous down-regulation of vimentin expression and a lack of coordination in collective behaviors, such as wound healing and acinus morphogenesis. Re-expression of vimentin in triple KO cells restored to a large extent normal persistence of single cell migration, suggesting that vimentin down-regulation contributes to the maintenance of the super-migrator phenotype in triple KO cells. Constant excessive production of branched actin at the cell cortex thus commits cells into a motile state through changes in gene expression.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping