Intracellular transport and cytotoxicity of the protein toxin ricin

Natalia Sowa-Rogozińska , Hanna Sominka , Jowita Nowakowska-Gołacka , Kirsten Sandvig , Monika Słomińska-Wojewódzka

Abstract

Ricin can be isolated from the seeds of the castor bean plant (Ricinus communis). It belongs to the ribosome-inactivating protein (RIP) family of toxins classified as a bio-threat agent due to its high toxicity, stability and availability. Ricin is a typical A-B toxin consisting of a single enzymatic A subunit (RTA) and a binding B subunit (RTB) joined by a single disulfide bond. RTA possesses an RNA N-glycosidase activity; it cleaves ribosomal RNA leading to the inhibition of protein synthesis. However, the mechanism of ricin-mediated cell death is quite complex, as a growing number of studies demonstrate that the inhibition of protein synthesis is not always correlated with long term ricin toxicity. To exert its cytotoxic effect, ricin A-chain has to be transported to the cytosol of the host cell. This translocation is preceded by endocytic uptake of the toxin and retrograde traffic through the trans-Golgi network (TGN) and the endoplasmic reticulum (ER). In this article, we describe intracellular trafficking of ricin with particular emphasis on host cell factors that facilitate this transport and contribute to ricin cytotoxicity in mammalian and yeast cells. The current understanding of the mechanisms of ricin-mediated cell death is discussed as well. We also comment on recent reports presenting medical applications for ricin and progress associated with the development of vaccines against this toxin.
Author Natalia Sowa-Rogozińska (FB / DMBG)
Natalia Sowa-Rogozińska,,
- Katedra Biologii i Genetyki Medycznej
, Hanna Sominka (FB / DMBG)
Hanna Sominka,,
- Katedra Biologii i Genetyki Medycznej
, Jowita Nowakowska-Gołacka (FB / DMBG)
Jowita Nowakowska-Gołacka,,
- Katedra Biologii i Genetyki Medycznej
, Kirsten Sandvig
Kirsten Sandvig,,
-
, Monika Słomińska-Wojewódzka (FB / DMBG)
Monika Słomińska-Wojewódzka,,
- Katedra Biologii i Genetyki Medycznej
Journal seriesToxins, ISSN 2072-6651, (N/A 100 pkt)
Issue year2019
Vol11
No6
Pages1-37
Publication size in sheets1.8
Article number350
Keywords in Englishricin, protein synthesis inhibition, apoptosis
ASJC Classification3005 Toxicology; 2307 Health, Toxicology and Mutagenesis
DOIDOI:10.3390/toxins11060350
URL https://doi.org/10.3390/toxins11060350
Languageen angielski
LicenseJournal (articles only); published final; Uznanie Autorstwa (CC-BY); with publication
Score (nominal)100
Score sourcejournalList
ScoreMinisterial score = 100.0, 28-01-2020, ArticleFromJournal
Publication indicators WoS Citations = 2; Scopus SNIP (Source Normalised Impact per Paper): 2017 = 1.136; WoS Impact Factor: 2018 = 3.895 (2) - 2018=4.009 (5)
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