Influence of Rho acitvating bacterial toxins on the regulation of Rho GTPase signaling networks

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Rho GTPases are small GTP binding proteins of the Ras supergene family, which are regulated in a GTPase cycle. Some bacterial toxins activate Rho proteins by deamidation, for example the family of cytotoxic necrotizing factors (CNFs). It encompasses 4 members: CNF1, CNF2 and CNF3 are produced by pathogenic Escherichia coli strains, CNFY by Yersinia pseudotuberculosis. In recent years, we have analyzed the CNFs in detail. We know how they are taken up and which set of Rho GTPases is activated by each family member. Additionally, we generated toxin chimeras with varying substrate specificity and now have a set of cell penetrating Rho activators, which we will use for analyzing Rho-dependent signaling pathways. Moreover, the toxins and toxin variants will help to understand the influence of the Rho signaling pathways among each other. A fundamental advantage of the toxins is that they activate Rho GTPases without over-expression of active mutants, which definitely destroys the cellular balance between the amount of Rho GTPases and GDI.