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PMID: 11553710 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

RhoA inactivation by p190RhoGAP regulates cell spreading and migration by promoting membrane protrusion and polarity.

Molecular biology of the cell ·Vol. 12 ·No. 9 ·2001-09-00 ·Pages 2711-20

Arthur WT, Burridge K

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.

MeSH Terms
Actins/metabolism Animals Cell Adhesion Cell Membrane/metabolism Cell Movement Cell Polarity Cell Size Cell Surface Extensions/metabolism Cytoskeleton/metabolism DNA-Binding Proteins Fibroblasts Guanine Nucleotide Exchange Factors/metabolism Microscopy, Fluorescence Models, Biological Nuclear Proteins/metabolism Rats Repressor Proteins rhoA GTP-Binding Protein/antagonists & inhibitors,metabolism
Chemicals
Actins Arhgap35 protein, rat DNA-Binding Proteins Guanine Nucleotide Exchange Factors Nuclear Proteins Repressor Proteins rhoA GTP-Binding Protein
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Arthur W T
Department of Cell and Developmental Biology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA. [email protected]
Burridge K
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.12.9.2711
Email
[email protected]
Published
2001-09-00
Pages
2711-20
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC59706
Subset
IM
Grants
NIGMS NIH HHS · R01 GM029860 · United States
NIGMS NIH HHS · GM29860 · United States
External Links
PubMed source DOI: 10.1091/mbc.12.9.2711 PMC Full Text View journal details
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