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"Switch to kill, switch to survive" – bacterial toxins modifying Rho GTPases

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Various bacterial protein toxins act on eukaryotic cells by targeting switches involved in cellular signalling and/or control of the cytoskeleton. Of particular importance as targets are molecular switches of the Rho GTPase family. The GTPase switches have crucial functions in innate and adapted immunity and play pivotal roles in the biology of infection, which explains their preferred targeting by toxins. The toxins activate or inactivate Rho GTPases by different modes of action. Cytotoxic necrotizing factors (CNFs) from E. coli and Yersinia species activate Rho GTPases by deamidation of a glutamine residue, which is involved in the switch-off mechanism of the GTPases. Activation of RhoA is caused by Pasteurella multocida toxin secondary to activation of the heterotrimeric G proteins Gq and G12/13. On the other hand, the Yersinia effector protein YopT, which acts as a cysteine-specific protease to cleave the lipid anchor of GTPases, inactivates Rho GTPases. C3 exotoxins inactivate RhoA, B and C by ADP-ribosylation at Asn41 thereby preventing activation of Rho, stabilizing the Rho-GDI complex and inhibiting signalling. Large clostridial toxins, including C. difficile toxin A and B, inactivate various Rho GTPases by glucosylation. The mode of action of C. difficile toxins and their structure-function relationship will be discussed in detail.

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Correspondence to K Aktories.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Aktories, K. "Switch to kill, switch to survive" – bacterial toxins modifying Rho GTPases. Cell Commun Signal 7, A41 (2009) doi:10.1186/1478-811X-7-S1-A41

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Keywords

  • Glutamine Residue
  • Protein Toxin
  • GTPase Family
  • Yersinia Species
  • Lipid Anchor