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Role of Phospholipase A2 in Retrograde Transport of Ricin
Centre for Cancer Biomedicine, Department of Biochemistry, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, 0310 Oslo, Norway
Department of Molecular Biosciences, University of Oslo, 0316 Oslo, Norway
* Author to whom correspondence should be addressed.
Received: 1 July 2011; in revised form: 25 August 2011 / Accepted: 16 September 2011 / Published: 23 September 2011
(This article belongs to the Special Issue Ricin Toxin
Abstract: 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
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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.
Klokk TI, Lingelem ABD, Myrann A-G, Sandvig K. Role of Phospholipase A2 in Retrograde Transport of Ricin. Toxins. 2011; 3(9):1203-1219.
Klokk, Tove Irene; Lingelem, Anne Berit Dyve; Myrann, Anne-Grethe; Sandvig, Kirsten. 2011. "Role of Phospholipase A2 in Retrograde Transport of Ricin." Toxins 3, no. 9: 1203-1219.