Spooner, Robert A. and Lord, Mike (2012) How ricin and shiga toxin reach the cytosol of target cells : retrotranslocation from the endoplasmic reticulum. Current Topics in Microbiology and Immunology, Vol.357 . pp. 19-40. doi:1007/82_2011_154 ISSN 0070-217X.

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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.

Item Type:	Journal Article
Subjects:	Q Science > QP Physiology
Divisions:	Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- )
Library of Congress Subject Headings (LCSH):	Ricin -- Physiological transport, Verocytotoxins -- Physiological transport, Endoplasmic reticulum
Journal or Publication Title:	Current Topics in Microbiology and Immunology
Publisher:	Springer New York LLC
ISSN:	0070-217X
Official Date:	2012
Dates:	Date Event 2012 Published
Volume:	Vol.357
Page Range:	pp. 19-40
DOI:	1007/82_2011_154
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Date of first compliant deposit:	1 August 2016
Date of first compliant Open Access:	1 August 2016
Funder:	Wellcome Trust (London, England), National Institutes of Health (U.S.) (NIH)
Grant number:	080566/Z/06/Z (Wellcome), 5U01AI65869-02 (NIH)

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