Interplay of RhoA and motility in the programmed spreading of daughter cells postmitosis.
Upon cortical retraction in mitosis, mammalian cells have a dramatically decreased physical association with their environment. Hence, mechanisms that prevent mitotic detachment and ensure appropriate positioning of the resulting daughter cells are critical for effective tissue morphogenesis and repair, and are the subject of this study. We find that, unlike low-motility cells, highly motile cells spread isotropically upon division and do not typically reoccupy their mother-cell footprint, and often even disseminate their mitotic cells. To elucidate these different motility-based phenotypes, we investigated their partial recapitulation and rescue using defined molecular perturbations. We show that activated RhoA is localized at the mitotic cell cortex, and Rho-associated kinase inhibition increases the degree of reoccupation of the mother-cell outline in highly motile cells. Conversely, we show that induction of motility in low-motility cells by RasV12 overexpression results in increased isotropic daughter-cell spreading. We thus propose that a balance between cortical retraction forces, which depend in part on RhoA activation, and substrate adhesion forces, which diminish with increasing motility rates, governs the integrity of mitotic actin retraction fibers and influences subsequent daughter-cell spreading. This balance of forces during mitosis has implications for cancer metastasis.
Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, Maryland, USA.
Prashant
P
Mali
Denis
D
Wirtz
Peter C
PC
Searson
D000199:Actins / Q000378:metabolism; D002448:Cell Adhesion; D002465:Cell Movement; D005353:Fibronectins / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis; D008954:Models, Biological; D050505:Mutant Proteins / Q000378:metabolism; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D013379:Substrate Specificity; D018631:ras Proteins / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D000199:Actins; D005353:Fibronectins; D050505:Mutant Proteins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D018631:ras Proteins; D020742:rhoA GTP-Binding Protein