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Ricin trafficking in cells
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Spooner, Robert A. and Lord, Mike (2015) Ricin trafficking in cells. Toxins, Volume 7 (Number 1). pp. 49-65. doi:10.3390/toxins7010049 ISSN 2072-6651.
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Official URL: http://dx.doi.org/10.3390/toxins7010049
Abstract
The heterodimeric plant toxin ricin binds exposed galactosyls at the cell surface of target mammalian cells, and, following endocytosis, is transported in vesicular carriers to the endoplasmic reticulum (ER). Subsequently, the cell-binding B chain (RTB) and the catalytic A chain (RTA) are separated reductively, RTA embeds in the ER membrane and then retrotranslocates (or dislocates) across this membrane. The protein conducting channels used by RTA are usually regarded as part of the ER-associated protein degradation system (ERAD) that removes misfolded proteins from the ER for destruction by the cytosolic proteasomes. However, unlike ERAD substrates, cytosolic RTA avoids destruction and folds into a catalytic conformation that inactivates its target ribosomes. Protein synthesis ceases, and subsequently the cells die apoptotically. This raises questions about how this protein avoids the pathways that are normally sanctioned for ER-dislocating substrates. In this review we focus on the molecular events that occur with non-tagged ricin and its isolated subunits at the ER–cytosol interface. This focus reveals that intra-membrane interactions of RTA may control its fate, an area that warrants further investigation.
Item Type: | Journal Article | ||||||||
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Subjects: | Q Science > QR Microbiology | ||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||||
Library of Congress Subject Headings (LCSH): | Ricin | ||||||||
Journal or Publication Title: | Toxins | ||||||||
Publisher: | MDPI Publishing | ||||||||
ISSN: | 2072-6651 | ||||||||
Official Date: | 9 January 2015 | ||||||||
Dates: |
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Volume: | Volume 7 | ||||||||
Number: | Number 1 | ||||||||
Page Range: | pp. 49-65 | ||||||||
DOI: | 10.3390/toxins7010049 | ||||||||
Status: | Peer Reviewed | ||||||||
Publication Status: | Published | ||||||||
Access rights to Published version: | Restricted or Subscription Access | ||||||||
Date of first compliant deposit: | 28 December 2015 | ||||||||
Date of first compliant Open Access: | 28 December 2015 | ||||||||
Funder: | Wellcome Trust (London, England) | ||||||||
Grant number: | 080566Z/06/Z (WT) |
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