Cholera toxin: A paradigm for multi-functional engagement of cellular mechanisms (Review)

  title={Cholera toxin: A paradigm for multi-functional engagement of cellular mechanisms (Review)},
  author={Lolke de Haan and Timothy Raymond Hirst},
  journal={Molecular Membrane Biology},
  pages={77 - 92}
Cholera toxin (Ctx) from Vibrio cholerae and its closely related homologue, heat-labile enterotoxin (Etx) from Escherichia coli have become superb tools for illuminating pathways of cellular trafficking and immune cell function. These bacterial protein toxins should be viewed as conglomerates of highly evolved, multi-functional elements equipped to engage the trafficking and signalling machineries of cells. Ctx and Etx are members of a larger family of A-B toxins of bacterial (and plant) origin… 
Vibrio cholerae: cholera toxin.
A Therapeutic Chemical Chaperone Inhibits Cholera Intoxication and Unfolding/Translocation of the Cholera Toxin A1 Subunit
It is shown by circular dichroism and fluorescence spectroscopy that exposure to 4-phenylbutyric acid (PBA) inhibited the thermal unfolding of CTA1, which blocked the ER-to-cytosol export of Cta1 and productive intoxication of either cultured cells or rat ileal loops.
Grape Extracts Inhibit Multiple Events in the Cell Biology of Cholera Intoxication
Two grape extracts currently sold as nutritional supplements inhibited CT and Escherichia coli heat-labile toxin activity against cultured cells and intestinal loops and disrupted the catalytic activity of CTA1.
Characterization of Fluorescent Chimeras of Cholera Toxin and Escherichia coli Heat-Labile Enterotoxins Produced by Use of the Twin Arginine Translocation System
Fluorescent fusion proteins were shown to assemble spontaneously and efficiently with the corresponding B polypeptides in the periplasm to form chimeric holotoxin-like molecules, and these chimeras bound to and entered cultured cells in a manner similar to native CT, LTI, or LTIIb.
Host Cell Chaperones Hsp70/Hsp90 and Peptidyl-Prolyl Cis/Trans Isomerases Are Required for the Membrane Translocation of Bacterial ADP-Ribosylating Toxins.
Bacterial ADP-ribosylating toxins are the causative agents for several severe human and animal diseases such as diphtheria, cholera, or enteric diseases. They display an AB-type structure: The
Cholera Toxin Interactions with Host Cell Stress Proteins
The intrinsic conformational instability of the CTA1 polypeptide drives host-toxin interactions related to the translocation event and involves both standard and atypical functions for a variety of host chaperones.
Modulation of Cholera Toxin Structure/Function by Hsp90
Hsp90 plays two key roles CT intoxication: it couples toxin refolding with toxin extraction from the ER, and it maintains the cytosolic toxin in a functional conformation.
Brefeldin A and Exo1 Completely Releave the Block of Cholera Toxin Action by a Dipeptide Metalloendoprotease Substrate
Cholera toxin (CT), the enterotoxin secreted by Vibrio cholerae classical as well as El Tor biotypes, is the major causative agent of the acute diarrheal disease of humans. CT and the Escherichia
An outer membrane channel protein of Mycobacterium tuberculosis with exotoxin activity
It is demonstrated that the M. tuberculosis protein Rv3903c (channel protein with necrosis-inducing toxin, CpnT), which forms a channel in the outer membrane and releases a toxic domain into the extracellular milieu, has a dual function in uptake of nutrients and induction of host cell death by M.culosis.
The Cholera Toxin A13 Subdomain Is Essential for Interaction with ADP-Ribosylation Factor 6 and Full Toxic Activity but Is Not Required for Translocation from the Endoplasmic Reticulum to the Cytosol
It is found that the A13 subdomain of CTA1 is important both for interaction with ARF6 and for full expression of enzyme activity in vivo and Surprisingly, however, the A 13 subdomain was not required for ERAD-mediated passage of Cta1 from the ER to the cytosol.


Mutant Escherichia coli Heat-Labile Toxin B Subunit That Separates Toxoid-Mediated Signaling and Immunomodulatory Action from Trafficking and Delivery Functions
EtxB(H57S) represents a novel tool for evaluating the complex cellular interactions and signaling events occurring after receptor interaction, as well as offering an alternative means of delivering attached peptides in the absence of the potent immunomodulatory signals induced by wild-type B subunits.
Structural Basis for the Differential Toxicity of Cholera Toxin and Escherichia coli Heat-labile Enterotoxin
A comparison of the in vitro stability of two hybrid toxins, differing only in this 10-amino acid segment, revealed that the Ctx A2-segment conferred a greater stability to the interaction between the A- and B-subunits than the corresponding segment from E TX A2.
Targeting of cholera toxin and Escherichia coli heat labile toxin in polarized epithelia: role of COOH-terminal KDEL
Evidence is provided that CT and LT interact directly with endogenous KDEL-receptors and imply that both toxins may require retrograde movement through Golgi cisternae and ER for efficient and maximal biologic activity.
Structure and function of cholera toxin and the related Escherichia coli heat-labile enterotoxin.
The recent elucidation of the three-dimensional structure of the heat-labile enterotoxin has provided an opportunity to examine and compare the correlations between structure and function of the two toxins, which may improve understanding of the disease process itself and illuminate the role of the toxin in studies of signal transduction and G-protein function.
A mutant cholera toxin B subunit that binds GM1- ganglioside but lacks immunomodulatory or toxic activity
  • A. Aman, S. Fraser, T. Hirst
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 2001
It is demonstrated that GM1 binding, contrary to expectation, is not sufficient to initiate toxin action, and the engineering and crystallographic structure of a mutant cholera toxin is reported, with a His to Ala substitution in the B subunit at position 57.
Proteolytic Activation of Cholera Toxin and Escherichia coli Labile Toxin by Entry into Host Epithelial Cells
T84 cells express a serine-type protease(s) fully sufficient for activating the A subunits of CT and LT, however, the protease is only accessible for activation when the toxin enters the cell via the apical membrane.
Modulation of B lymphocyte signalling by the B subunit of Escherichia coli heat-labile enterotoxin.
It is demonstrated that receptor binding by EtxB triggers multiple signalling pathways in B cells that regulate the expression of key cell surface molecules and can trigger up-regulated expression of class II MHC and CD25 on purified populations of B lymphocytes.
Orientation of cholera toxin bound to target cells.
It is proposed that the holotoxin binds with its A subunit facing away from the membrane and must enter the cell in order for A1 to be released, gain access to Gs alpha, and activate adenylylcyclase.
ARF binds the C-terminal region of the Escherichia coli heat-labile toxin (LTA1) and competes for the binding of LTA2.
The possibility that the LTA(2) subunit may function in cells as a partial ARF mimetic to compete for the binding of ARF to LTA (1) or regulate aspects of the toxin's transport from the cell surface to the ER is discussed.