Citation

Spooner RA, Lord JM. Curr. Top. Microbiol. Immunol. 2012; 357: 19-40.

Affiliation

School of Life Sciences, University of Warwick, Coventry, CV4 7AL, UK, R.A.Spooner@warwick.ac.uk.

Copyright

(Copyright © 2012, Holtzbrinck Springer Nature Publishing Group)

DOI

10.1007/82_2011_154

PMID

21761287

Abstract

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.

Language: en