Pore formation by tetanus toxin, its chain and fragments in neuronal membranes and evaluation of the underlying motifs in the structure of the toxin molecule

@article{Beise2004PoreFB,
  title={Pore formation by tetanus toxin, its chain and fragments in neuronal membranes and evaluation of the underlying motifs in the structure of the toxin molecule},
  author={Joachim Beise and Josef Hahnen and B Andersen-Beckh and Florian Dreyer},
  journal={Naunyn-Schmiedeberg's Archives of Pharmacology},
  year={2004},
  volume={349},
  pages={66-73}
}
The pore-forming activity of tetanus toxin, its chains and fragments was studied on membrane patches from spinal cord neurons of fetal mice using the outside-out patch-clamp configuration.1. The dichain tetanus toxin forms pores at pH 5, but not at pH 7.4. The elementary pore conductance is 38.4±1.1 pS and nonselective for small cations. The open probability of the pores is voltage-dependent and increases with membrane depolarisation. The pores activate at +80 mV with a time constant of about… 

Gating and permeability of ion channels produced by botulinum toxin types A and E in PC12 cell membranes.

  • R. Sheridan
  • Biology
    Toxicon : official journal of the International Society on Toxinology
  • 1998

Double anchorage to the membrane and intact inter‐chain disulfide bond are required for the low pH induced entry of tetanus and botulinum neurotoxins into neurons

This study found that the neurotoxin has to be bound to the membrane via at least two anchorage sites in order for a productive low‐pH induced structural change to take place, and proposed a stepwise sequence of molecular events that lead from toxin binding to membrane insertion.

Acidification of the cytosol inhibits the uptake of tetanus toxin in NG108-15 and NBr-10A neurohybridoma cells

Acidification of the extracellular environment has been shown to facilitate the uptake of tetanus toxin, and under pH clamp conditions, this effect is stronger than the simultaneous retardation of the toxin uptake by acidification also of the cytosol.

The entry of tetanus and botulinum neurotoxins into neurons

This study found that the neurotoxin has to be bound to the membrane via at least two anchorage sites in order for a productive low-pH induced structural change to take place, and indicates auranofin, as a possible basis for the design of novel inhibitors of these neurotoxins.

In situ scanning probe microscopy studies of tetanus toxin-membrane interactions.

The results show that Tet C preferentially binds to the surface of fluid phase domains within biphasic membranes containing G(T1b) and that with an extended incubation period these interactions lead to dramatic changes in the morphology of the lipid bilayer, including the formation of 40-80 nm diameter circular cavities.

[Therapeutic applications of pore-forming lytic toxins: potential use of Escherichia coli alpha-hemolysin].

Many infectious bacteria export soluble proteins which can damage the plasma membrane of eukaryotic cells, and these molecules increase the cell susceptibility to chemotherapy and also can be employed to destroy specifically cancer cells.

Bacterial protein toxins and cell vesicle trafficking

A group of bacterial protein toxins interfere with vesicular trafficking inside cells and cleave the three SNARE proteins: VAMP, SNAP-25 and syntaxin, and this selective proteolysis results in a blockade of exocytosis.

Passage of botulinum neurotoxin across intestinal barrier

BoNT/A inhibits smooth muscle contractions and fluorescent Hc/A migrates across mucosa, through some crypt cells, to submucosa and musculosa where it targets certain nerve endings, mostly cholinergic, in an intestinal epithelium model.

CLOSTRIDIAL NEUROTOXINS

Important questions on the mechanism responsible for the binding specificity and for the targeting of TeNT and BoNTs remain to be addressed, and this novel information would enables us to use CNTs more efficiently as therapeutic tools in neuronal disorders.

References

SHOWING 1-10 OF 61 REFERENCES

Pore formation by Staphylococcus aureus alpha-toxin in lipid bilayers

The analysis of single conductance events shows that a heterogeneous population of pores exist and that smaller channels are preferred at low temperature, attribute this heterogeneity to the existence of pores resulting from the aggregation of different numbers of monomers.

Low pH induces a hydrophobic domain in the tetanus toxin molecule.

It is suggested that, as for diphtheria toxin, entry of tetanus toxin into an acidic compartment of target cells might be required for the expression of its biological activity.

Increase of permeability of synaptosomes and liposomes by the heavy chain of tetanus toxin.

Ionic channels formed byStaphylococcus aureus alpha-toxin: Voltage-dependent inhibition by divalent and trivalent cations

A voltage-gated inactivation mechanism is proposed which involves the binding of two polyvalent cations to the channel, one in the open and one in a closed configuration, and which can explain voltage, dose and time dependence of the inactivation.

Tetanus toxin is a zinc protein and its inhibition of neurotransmitter release and protease activity depend on zinc.

The present findings indicate that tetanus toxin, and possibly also the botulinum neurotoxins, are metalloproteases and that they block neurotransmitter release via this protease activity.

At least three sequential steps are involved in the tetanus toxin-induced block of neuromuscular transmission

The kinetic aspects of the block were studied in vitro on the mouse phrenic nerve-hemidiaphragm exposed to toxin in order to suggest the involvement of a phase transition rather than of an enzymatic activity of the toxin.
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