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National Institute of Environmental Health Sciences

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Publication Detail

Title: RhoA is down-regulated at cell-cell contacts via p190RhoGAP-B in response to tensional homeostasis.

Authors: Ponik, Suzanne M; Trier, Steven M; Wozniak, Michele A; Eliceiri, Kevin W; Keely, Patricia J

Published In Mol Biol Cell, (2013 Jun)

Abstract: Breast epithelial cells cultured in three-dimensional (3D) collagen gels undergo ductal morphogenesis when the gel is compliant and they can achieve tensional homeostasis. We previously showed that this process requires down-regulation of Rho in compliant collagen gels, but the mechanism remains undefined. In this study, we find that p190RhoGAP-B, but not p190RhoGAP-A, mediates down-regulation of RhoA activity and ductal morphogenesis in T47D cells cultured in compliant 3D collagen gels. In addition, both RhoA and p190RhoGAP-B colocalize with p120-catenin at sites of cell-cell contact. The association between p190RhoGAP-B and p120-catenin is regulated by matrix compliance such that it increases in compliant vs. rigid collagen gels. Furthermore, knockdown of p120-catenin disrupts ductal morphogenesis, disregulates RhoA activity, and results in loss of p190B at cell-cell contacts. Consistent with these findings, using a RhoA-specific FRET biosensor (RhoA-FLARE.sc), we determined spatial RhoA activity to be significantly decreased at cell-cell contacts versus cell-ECM adhesions, and, of importance, spatial RhoA activity is regulated by p190B. This finding suggests that RhoA exists as an inactive pool at cell-cell contacts and is recruited to cell-ECM contacts within stiff matrices. Overall, these results demonstrate that RhoA is down-regulated at cell-cell contacts through p190RhoGAP-B, which is localized to cell-cell contacts by association with p120-catenin that is regulated by tensional homeostasis.

PubMed ID: 23552690 Exiting the NIEHS site

MeSH Terms: Catenins/antagonists & inhibitors; Catenins/genetics; Catenins/metabolism; Cell Adhesion; Cell Communication; Cell Culture Techniques; Cell Line; Collagen/chemistry; Epithelial Cells/cytology; Epithelial Cells/metabolism*; Female; Fluorescence Recovery After Photobleaching; GTPase-Activating Proteins/genetics*; GTPase-Activating Proteins/metabolism; Gels; Gene Expression Regulation; Guanine Nucleotide Exchange Factors/genetics*; Guanine Nucleotide Exchange Factors/metabolism; Humans; Intercellular Junctions/metabolism*; Intercellular Junctions/ultrastructure; Mammary Glands, Human/cytology; Mammary Glands, Human/metabolism*; Pliability; Repressor Proteins/genetics*; Repressor Proteins/metabolism; Signal Transduction; Surface Tension

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