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How ricin and shiga toxin reach the cytosol of target cells : retrotranslocation from the endoplasmic reticulum
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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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Official URL: http://dx.doi.org/1007/82_2011_154
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 | ||||
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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: |
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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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