ARHGAP18, a GTPase-activating protein for RhoA, controls cell shape, spreading, and motility
Open Access
- 15 October 2011
- journal article
- Published by American Society for Cell Biology (ASCB) in Molecular Biology of the Cell
- Vol. 22 (20), 3840-3852
- https://doi.org/10.1091/mbc.e11-04-0364
Abstract
Rho GTPases are molecular switches that transmit biochemical signals in response to extracellular stimuli to elicit changes in the actin cytoskeleton. Rho GTPases cycle between an active, GTP-bound state and an inactive, GDP-bound state. These states are regulated by two distinct families of proteins—guanine nucleotide exchange factors and GTPase-activating proteins (GAPs). We studied the role of a previously uncharacterized GAP, ARHGAP18 (MacGAP). Overexpression of ARHGAP18 suppressed the activity of RhoA and disrupted stress fiber formation. Conversely, silencing of ARHGAP18 by small interfering RNA transfection–enhanced stress fiber formation and induced rounding of cells. We examined the role of ARHGAP18 in cell spreading and migration. Immunofluorescence analysis revealed that ARHGAP18 was localized to the leading edge during cell spreading and migration. ARHGAP18-knockdown cells showed impaired spreading, premature formation of stress fibers, and sustained activation of RhoA upon cell attachment. In addition, knockdown and overexpression of ARHGAP18 resulted in the inhibition and promotion of cell migration, respectively. Furthermore, ARHGAP18 was required for the polarization of cells for migration. Our results define ARHGAP18 as one of the crucial factors for the regulation of RhoA for the control of cell shape, spreading, and migration.Keywords
This publication has 48 references indexed in Scilit:
- The Roles of Two Distinct Regions of PINCH-1 in the Regulation of Cell Attachment and SpreadingMolecular Biology of the Cell, 2010
- Rho‐kinase/ROCK: A key regulator of the cytoskeleton and cell polarityCytoskeleton, 2010
- Coordination of Rho GTPase activities during cell protrusionNature, 2009
- GEFs and GAPs: Critical Elements in the Control of Small G ProteinsCell, 2007
- Rho activation at a glanceJournal of Cell Science, 2007
- Cell Migration: Integrating Signals from Front to BackScience, 2003
- Cdc42 regulates GSK-3β and adenomatous polyposis coli to control cell polarityNature, 2003
- Rho-stimulated contractility drives the formation of stress fibers and focal adhesions.The Journal of cell biology, 1996
- Integrins: Emerging Paradigms of Signal TransductionAnnual Review of Cell and Developmental Biology, 1995
- Integrins: Versatility, modulation, and signaling in cell adhesionCell, 1992