Interplay of RhoA and motility in the programmed spreading of daughter cells postmitosis

Prashant Mali, Denis Wirtz, Peter C. Searson

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3526-3534
Number of pages9
JournalBiophysical Journal
Volume99
Issue number11
DOIs
StatePublished - Dec 1 2010

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Mitosis
Cell Movement
Stem Cells
rho-Associated Kinases
Morphogenesis
Actins
Neoplasm Metastasis
Phenotype
Neoplasms

ASJC Scopus subject areas

  • Biophysics

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Interplay of RhoA and motility in the programmed spreading of daughter cells postmitosis. / Mali, Prashant; Wirtz, Denis; Searson, Peter C.

In: Biophysical Journal, Vol. 99, No. 11, 01.12.2010, p. 3526-3534.

Research output: Contribution to journalArticle

Mali, Prashant ; Wirtz, Denis ; Searson, Peter C. / Interplay of RhoA and motility in the programmed spreading of daughter cells postmitosis. In: Biophysical Journal. 2010 ; Vol. 99, No. 11. pp. 3526-3534.
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