A number of protein toxins bind at the surface of mammalian cells and after endocytosis traffic to the endoplasmic reticulum, where the toxic A chains are liberated from the holotoxin. The free A chains are then dislocated, or retrotranslocated, across the ER membrane into the cytosol. Here, in contrast to ER substrates destined for proteasomal destruction, they undergo folding to a catalytic conformation and subsequently inactivate their cytosolic targets. These toxins therefore provide toxic probes for testing the molecular requirements for retrograde trafficking, the ER processes that prepare the toxic A chains for transmembrane transport, the dislocation step itself and for the post-dislocation folding that results in catalytic activity. We describe here the dislocation of ricin A chain and Shiga toxin A chain, but also consider cholera toxin which bears a superficial structural resemblance to Shiga toxin. Recent studies not only describe how these proteins breach the ER membrane, but also reveal aspects of a fundamental cell biological process, that of ER-cytosol dislocation. © 2011 Springer-Verlag Berlin Heidelberg.
CITATION STYLE
Spooner, R. A., & Lord, J. M. (2012). How ricin and Shiga toxin reach the cytosol of target cells: Retrotranslocation from the endoplasmic reticulum. Current Topics in Microbiology and Immunology, 357, 19–40. https://doi.org/10.1007/82_2011_154
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