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Bacterial toxins inhibiting or activating small GTP-binding proteins

P Boquet1

  • 1Institut National de la Santé et de la Recherche Médicale (INSERM), Faculté de Médecine, Nice, France. boquet@unice.fr

Annals of the New York Academy of Sciences
|February 10, 2000
PubMed

Insights

Bacterial toxins target Rho GTPases, altering their function through ADP-ribosylation, glucosylation, or deamidation. These modifications disrupt cellular signaling by preventing GTPase membrane recruitment or effector binding.

Area of Science:

  • Microbiology
  • Cell Biology
  • Biochemistry

Background:

  • Small GTPases, including Ras and Rho families, are crucial regulators of cellular processes.
  • Specific amino acid residues in switch 1 and switch 2 domains are vulnerable to bacterial toxin modification.
  • Rho GTPases play key roles in cell membrane dynamics and downstream signaling pathways.

Purpose of the Study:

  • To review the molecular mechanisms by which bacterial toxins target and modify Rho GTPases.
  • To highlight the diverse enzymatic activities employed by toxins to disrupt Rho GTPase function.
  • To discuss the implications of these modifications on cellular signaling.

Main Methods:

  • Analysis of published literature on bacterial toxins affecting Rho GTPases.
  • Description of enzymatic modifications: ADP-ribosylation, glucosylation, and deamidation.
  • Identification of specific target amino acids and their functional consequences.

Main Results:

  • Exoenzyme C3 (Clostridium botulinum) ADP-ribosylates Rho at R43, inhibiting membrane recruitment.
  • Clostridium difficile toxin B and Clostridium sordellii lethal toxin glucosylate Rho, Rac, and Cdc42, blocking effector binding.
  • Cytotoxic necrotizing factor 1 (CNF1) deamidates Rho at Q63, preventing GTPase activity and causing permanent activation.

Conclusions:

  • Rho GTPases are targeted by at least three distinct bacterial toxin activities.
  • Toxin-mediated modifications effectively inhibit or constitutively activate Rho GTPases, leading to cellular dysfunction.
  • Understanding these mechanisms provides insights into bacterial pathogenesis and host-pathogen interactions.

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