Next Article in Journal
Overexpression of the Trichoderma brevicompactum tri5 Gene: Effect on the Expression of the Trichodermin Biosynthetic Genes and on Tomato Seedlings
Next Article in Special Issue
Structure-Based Design of Ricin Inhibitors
Previous Article in Journal
The Potential Contributions of Lethal and Edema Toxins to the Pathogenesis of Anthrax Associated Shock
Previous Article in Special Issue
Passive and Active Vaccination Strategies to Prevent Ricin Poisoning
Toxins 2011, 3(9), 1203-1219; doi:10.3390/toxins3091203

Role of Phospholipase A2 in Retrograde Transport of Ricin

1 Centre for Cancer Biomedicine, Department of Biochemistry, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, 0310 Oslo, Norway 2 Department of Molecular Biosciences, University of Oslo, 0316 Oslo, Norway
* Author to whom correspondence should be addressed.
Received: 1 July 2011 / Revised: 25 August 2011 / Accepted: 16 September 2011 / Published: 23 September 2011
(This article belongs to the Special Issue Ricin Toxin)
View Full-Text   |   Download PDF [1972 KB, uploaded 23 September 2011]   |   Browse Figures


Ricin is a protein toxin classified as a bioterror agent, for which there are no known treatment options available after intoxication. It is composed of an enzymatically active A-chain connected by a disulfide bond to a cell binding B-chain. After internalization by endocytosis, ricin is transported retrogradely to the Golgi and ER, from where the ricin A-chain is translocated to the cytosol where it inhibits protein synthesis and thus induces cell death. We have identified cytoplasmic phospholipase A2 (PLA2) as an important factor in ricin retrograde transport. Inhibition of PLA2 protects against ricin challenge, however the toxin can still be endocytosed and transported to the Golgi. Interestingly, ricin transport from the Golgi to the ER is strongly impaired in response to PLA2 inhibition. Confocal microscopy analysis shows that ricin is still colocalized with the trans-Golgi marker TGN46 in the presence of PLA2 inhibitor, but less is colocalized with the cis-Golgi marker GM130. We propose that PLA2 inhibition results in impaired ricin transport through the Golgi stack, thus preventing it from reaching the ER. Consequently, ricin cannot be translocated to the cytosol to exert its toxic action.
Keywords: ricin; retrograde transport; phospholipase A2; Golgi; toxin ricin; retrograde transport; phospholipase A2; Golgi; toxin
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Share & Cite This Article

Further Mendeley | CiteULike
Export to BibTeX |
MDPI and ACS Style

Klokk, T.I.; Lingelem, A.B.D.; Myrann, A.-G.; Sandvig, K. Role of Phospholipase A2 in Retrograde Transport of Ricin. Toxins 2011, 3, 1203-1219.

View more citation formats

Related Articles

Article Metrics

For more information on the journal, click here


Cited By

[Return to top]
Toxins EISSN 2072-6651 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert