Format

Send to

Choose Destination
Toxins (Basel). 2019 Jun 18;11(6). pii: E350. doi: 10.3390/toxins11060350.

Intracellular Transport and Cytotoxicity of the Protein Toxin Ricin.

Author information

1
Department of Medical Biology and Genetics, Faculty of Biology, University of Gdańsk, Wita Stwosza 59, 80-308 Gdańsk, Poland. natalia.sowa@phdstud.ug.edu.pl.
2
Department of Medical Biology and Genetics, Faculty of Biology, University of Gdańsk, Wita Stwosza 59, 80-308 Gdańsk, Poland. hanna.sominka@phdstud.ug.edu.pl.
3
Department of Medical Biology and Genetics, Faculty of Biology, University of Gdańsk, Wita Stwosza 59, 80-308 Gdańsk, Poland. jowita.nowakowska@phdstud.ug.edu.pl.
4
Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, 0379 Oslo, Norway. kirsten.sandvig@ibv.uio.no.
5
Faculty of Mathematics and Natural Sciences, Department of Biosciences, University of Oslo, 0316 Oslo, Norway. kirsten.sandvig@ibv.uio.no.
6
Department of Medical Biology and Genetics, Faculty of Biology, University of Gdańsk, Wita Stwosza 59, 80-308 Gdańsk, Poland. monika.slominska@biol.ug.edu.pl.

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.

KEYWORDS:

apoptosis; protein synthesis inhibition; ricin

PMID:
31216687
DOI:
10.3390/toxins11060350
Free full text

Supplemental Content

Full text links

Icon for Multidisciplinary Digital Publishing Institute (MDPI) Icon for Norwegian BIBSYS system
Loading ...
Support Center