Crossref journal-article
American Society for Cell Biology (ASCB)
Molecular Biology of the Cell (1076)
Abstract

The binding of extracellular matrix proteins to integrins triggers rearrangements in the actin cytoskeleton by regulating the Rho family of small GTPases. The signaling events that mediate changes in the activity of Rho proteins in response to the extracellular matrix remain largely unknown. We have demonstrated in previous studies that integrin signaling transiently suppresses RhoA activity through stimulation of p190RhoGAP. Here, we investigated the biological significance of adhesion-dependent RhoA inactivation by manipulating p190RhoGAP signaling in Rat1 fibroblasts. The inhibition of RhoA activity that is induced transiently by adhesion was antagonized by expression of dominant negative p190RhoGAP. This resulted in impaired cell spreading on a fibronectin substrate, reduced cell protrusion, and premature assembly of stress fibers. Conversely, overexpression of p190RhoGAP augmented cell spreading. Dominant negative p190RhoGAP elevated RhoA activity in cells on fibronectin and inhibited migration, whereas overexpression of the wild-type GAP decreased RhoA activity, promoted the formation of membrane protrusions, and enhanced motility. Cells expressing dominant negative p190RhoGAP, but not control cells or cells overexpressing the wild-type GAP, were unable to establish polarity in the direction of migration. Taken together, these data demonstrate that integrin-triggered RhoA inhibition by p190RhoGAP enhances spreading and migration by regulating cell protrusion and polarity.

Bibliography

Arthur, W. T., & Burridge, K. (2001). RhoA Inactivation by p190RhoGAP Regulates Cell Spreading and Migration by Promoting Membrane Protrusion and Polarity. Molecular Biology of the Cell, 12(9), 2711–2720.

Authors 2
  1. William T. Arthur (first)
  2. Keith Burridge (additional)
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Dates
Type When
Created 12 years, 1 month ago (July 2, 2013, 8:20 p.m.)
Deposited 3 years, 6 months ago (Feb. 26, 2022, 9:46 p.m.)
Indexed 3 weeks, 1 day ago (Aug. 6, 2025, 9:25 a.m.)
Issued 23 years, 11 months ago (Sept. 1, 2001)
Published 23 years, 11 months ago (Sept. 1, 2001)
Published Print 23 years, 11 months ago (Sept. 1, 2001)
Funders 0

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@article{Arthur_2001, title={RhoA Inactivation by p190RhoGAP Regulates Cell Spreading and Migration by Promoting Membrane Protrusion and Polarity}, volume={12}, ISSN={1939-4586}, url={http://dx.doi.org/10.1091/mbc.12.9.2711}, DOI={10.1091/mbc.12.9.2711}, number={9}, journal={Molecular Biology of the Cell}, publisher={American Society for Cell Biology (ASCB)}, author={Arthur, William T. and Burridge, Keith}, editor={Beckerle, Mary C.}, year={2001}, month=sep, pages={2711–2720} }