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RhoA is required for cortical retraction and rigidity during mitotic cell rounding.

Maddox AS, Burridge K - J. Cell Biol. (2003)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell and Developmental Biology and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA. akshaub@med.unc.edu

ABSTRACT
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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RhoA and Rho-kinase are required for actin reorganization, cortical rigidity, and cortical retraction during mitotic cell rounding. Black arrows denote direct or indirect stimulation as shown here or in the literature. Gray arrows represent possible causal relationships. Black lines followed by bars denote inhibition.
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fig7: RhoA and Rho-kinase are required for actin reorganization, cortical rigidity, and cortical retraction during mitotic cell rounding. Black arrows denote direct or indirect stimulation as shown here or in the literature. Gray arrows represent possible causal relationships. Black lines followed by bars denote inhibition.

Mentions: In this paper, we show that RhoA is required for cortical retraction and rigidity as cells enter mitosis (results summarized in Fig. 7). The idea that RhoA regulates cortical rigidity is supported by several published observations. Treatment of interphase cells with C3 toxin causes a collapse of the spread morphology and the exposure of thin retraction fibers that branch and bleb (Rubin et al., 1988; Chardin et al., 1989). Our observation that RhoA is required for cortical rigidity during mitosis is also consistent with the finding that epithelial cells injected with C3 in prophase of mitosis appear to increase greatly in area as, presumably, they are stretched by neighboring cells (O'Connell et al., 1999).


RhoA is required for cortical retraction and rigidity during mitotic cell rounding.

Maddox AS, Burridge K - J. Cell Biol. (2003)

RhoA and Rho-kinase are required for actin reorganization, cortical rigidity, and cortical retraction during mitotic cell rounding. Black arrows denote direct or indirect stimulation as shown here or in the literature. Gray arrows represent possible causal relationships. Black lines followed by bars denote inhibition.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2172639&req=5

fig7: RhoA and Rho-kinase are required for actin reorganization, cortical rigidity, and cortical retraction during mitotic cell rounding. Black arrows denote direct or indirect stimulation as shown here or in the literature. Gray arrows represent possible causal relationships. Black lines followed by bars denote inhibition.
Mentions: In this paper, we show that RhoA is required for cortical retraction and rigidity as cells enter mitosis (results summarized in Fig. 7). The idea that RhoA regulates cortical rigidity is supported by several published observations. Treatment of interphase cells with C3 toxin causes a collapse of the spread morphology and the exposure of thin retraction fibers that branch and bleb (Rubin et al., 1988; Chardin et al., 1989). Our observation that RhoA is required for cortical rigidity during mitosis is also consistent with the finding that epithelial cells injected with C3 in prophase of mitosis appear to increase greatly in area as, presumably, they are stretched by neighboring cells (O'Connell et al., 1999).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell and Developmental Biology and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA. akshaub@med.unc.edu

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus