Rac1 inactivation by lethal toxin from Clostridium sordellii modifies focal adhesions upstream of actin depolymerization

Cell Microbiol. 2010 Feb;12(2):217-32. doi: 10.1111/j.1462-5822.2009.01392.x. Epub 2009 Oct 13.


Inactivation of different small GTPases upon their glucosylation by lethal toxin from Clostridium sordellii strain IP82 (LT-82) is already known to lead to cell rounding, adherens junction (AJ) disorganization and actin depolymerization. In the present work, we observed that LT-82 induces a rapid dephosphorylation of paxillin, a protein regulating focal adhesion (FA), independently of inactivation of paxillin kinases such as Src, Fak and Pyk2. Among the small GTPases inactivated by this toxin, including Rac, Ras, Rap and Ral, we identified Rac1, as responsible for paxillin dephosphorylation using cells overexpressing Rac1(V12). Rac1 inactivation by LT-82 modifies interactions between proteins from AJ and FA complexes as shown by pull-down assays. We showed that in Triton X-100-insoluble membrane proteins from these complexes, namely E-cadherin, beta-catenin, p120-catenin and talin, are decreased upon LT-82 intoxication, a treatment that also induces a rapid decrease in cell phosphoinositide content. Therefore, we proposed that Rac inactivation by LT-82 alters phosphoinositide metabolism leading to FA and AJ complex disorganization and actin depolymerization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism*
  • Bacterial Toxins / pharmacology*
  • Clostridium sordellii / drug effects*
  • Clostridium sordellii / metabolism*
  • Electrophoresis, Polyacrylamide Gel
  • Focal Adhesions / drug effects*
  • Focal Adhesions / metabolism*
  • HeLa Cells
  • Humans
  • Immunoblotting
  • Immunoprecipitation
  • Microscopy, Confocal
  • Microscopy, Phase-Contrast
  • Protein Binding / drug effects
  • rac1 GTP-Binding Protein / metabolism*


  • Actins
  • Bacterial Toxins
  • lethal toxin LT, Clostridium sordellii
  • rac1 GTP-Binding Protein