Increased Cell-Matrix Adhesion upon Constitutive Activation of Rho Proteins by Cytotoxic Necrotizing Factors from E. coli and Y. pseudotuberculosis.pdfVIP

Hindawi Publishing Corporation Journal of Signal Transduction Volume 2012, Article ID 570183, 10 pages doi:10.1155/2012/570183 Research Article Increased Cell-Matrix Adhesion upon Constitutive Activation of Rho Proteins by Cytotoxic Necrotizing Factors from E. coli and Y. pseudotuberculosis Martin May,1 Tanja Kolbe,1 Tianbang Wang,1 Gudula Schmidt,2 and Harald Genth1 1 Institute for Toxicology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany 2 Institute for Experimental and Clinical Pharmacology and Toxicology, University of Freiburg, 79104 Freiburg, Germany Correspondence should be addressed to Harald Genth, genth.harald@mh-hannover.de Received 28 March 2012; Accepted 3 June 2012 Academic Editor: Kris DeMali Copyright © 2012 Martin May et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Cytotoxic necrotizing factors (CNFs) encompass a class of autotransporter toxins produced by uropathogenic E. coli (CNF1) or Y. pseudotuberculosis (CNFy). CNF toxins deamidate and thereby constitutively activate RhoA, Rac1, and Cdc42. In this study, the effects of CNF1 on cell-matrix adhesion are analysed using functional cell-adhesion assays. CNF1 strongly increased cell-matrix binding of suspended Hela cells and decreased the susceptibly of cells to trypsin-induced cell detachment. Increased cell-matrix binding was also observed upon treatment of Hela cells with isomeric CNFy, that specifically deamidates RhoA. Increased cell- matrix binding thus appears to depend on RhoA deamidation. In contrast, increased cell spreading was specifically observed upon CNF1 treatment, suggesting that it rather dep