Mitotic cell rounding is the process of cell shape change in which a flat interphase cell becomes spherical at the onset of mitosis. Rearrangement of the actin cytoskeleton, de-adhesion, and an increase in cortical rigidity accompany mitotic cell rounding. The molecular mechanisms that contribute to this process have not been defined. We show that RhoA is required for cortical retraction but not de-adhesion during mitotic cell rounding. The mitotic increase in cortical rigidity also requires RhoA, suggesting that increases in cortical rigidity and cortical retraction are linked processes. Rho-kinase is also required for mitotic cortical retraction and rigidity, indicating that the effects of RhoA on cell rounding are mediated through this effector. Consistent with a role for RhoA during mitotic entry, RhoA activity is elevated in rounded, preanaphase mitotic cells. The activity of the RhoA inhibitor p190RhoGAP is decreased due to its serine/threonine phosphorylation at this time. Cumulatively, these results suggest that the mitotic increase in RhoA activity leads to rearrangements of the cortical actin cytoskeleton that promote cortical rigidity, resulting in mitotic cell rounding.
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20 January 2003
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January 21 2003
RhoA is required for cortical retraction and rigidity during mitotic cell rounding
Amy Shaub Maddox,
Amy Shaub Maddox
Department of Cell and Developmental Biology and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599
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Keith Burridge
Keith Burridge
Department of Cell and Developmental Biology and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599
Search for other works by this author on:
Amy Shaub Maddox
Department of Cell and Developmental Biology and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599
Keith Burridge
Department of Cell and Developmental Biology and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599
Address correspondence to Amy Shaub Maddox, 12-026 Lineberger, UNC-CH Chapel Hill, NC 27599. Tel.: (919) 966-5783. Fax: (919) 966-1856. E-mail: [email protected]
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Abbreviations used in this paper: GAP, GTPase activating protein; GEF, guanine nucleotide exchange factor; LIMK, LIM-kinase; MLC, myosin II regulatory light chain; PP1, protein phosphatase 1.
Received:
July 24 2002
Revision Received:
December 11 2002
Accepted:
December 12 2002
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2003
J Cell Biol (2003) 160 (2): 255–265.
Article history
Received:
July 24 2002
Revision Received:
December 11 2002
Accepted:
December 12 2002
Citation
Amy Shaub Maddox, Keith Burridge; RhoA is required for cortical retraction and rigidity during mitotic cell rounding . J Cell Biol 20 January 2003; 160 (2): 255–265. doi: https://doi.org/10.1083/jcb.200207130
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