To be helped or not helped, that is the question.

Emmanuel Lemichez,Patrice Boquet

doi:10.1083/jcb.200303032

Abstract

Diphtheria toxin (DT)* is the paradigm of the powerful A-B toxins. These bacterial poisons bind to cells, are endocytosed, and inject their catalytic domain into the cytosol causing the irreversible modification of a key component of the the host cellular machinery. The mechanism by which the hydrophilic enzymatic fragment of DT crosses the endosomal membrane and is released into the cytosol remains controversial. In this issue, Ratts et al. (2003) demonstrate that delivery of the DT catalytic domain from the lumen of purified early endosomes to the external medium requires the addition of a cytosolic translocation factor complex composed in part of Hsp90 and thioredoxin reductase.

Highlights

Diphtheria toxin (DT)* is the paradigm of the powerful A-B toxins
The group of John Murphy (Ratts et al, 2003) provides evidence that the translocation of DT catalytic fragment (DT-C) out of purified early endosomes is not an autonomous mechanism performed by the toxin itself, as previously suggested (Oh et al, 1999), but requires host cellular factors
Studies performed with artificial planar lipid bilayers and unilammelar liposomes brought forward the idea that DT-T domain insertion into lipidic membranes at low pH is sufficient to allow DT-C to flip from the cis to the trans side of the leaflet (Oh et al, 1999)

Summary

Introduction

Diphtheria toxin (DT)* is the paradigm of the powerful A-B toxins. These bacterial poisons bind to cells, are endocytosed, and inject their catalytic domain into the cytosol causing the irreversible modification of a key component of the the host cellular machinery. The group of John Murphy (Ratts et al, 2003) provides evidence that the translocation of DT catalytic fragment (DT-C) out of purified early endosomes is not an autonomous mechanism performed by the toxin itself, as previously suggested (Oh et al, 1999), but requires host cellular factors.

Results

Conclusion