Mechanisms involved in retrotranslocation of ricin from the endoplasmic reticulum to the cytosol

Ricin is a plant toxin produced in the seeds of the castor oil plant Ricinuscommunis. After endocytosis, the toxin is transported in a retrograde manner tothe endoplasmic reticulum (ER) via the trans-Golgi Network (TGN) before it isretrotranslocated to the cytosol where it exerts its cytotoxic effect by inhibitingprotein synthesis. Proteins that are misfolded in the ER are transported to thecytosol for degradation in a process known as ER-associated degradation(ERAD). Ricin is thought to exploit this mechanism to gain access to the cytosol.The mammalian Derlin-proteins are components of the ERAD machinery, andDerlin-3 has been shown to promote the retrotranslocation of misfoldedglycoproteins to the cytosol for degradation. In the present study, we haveinvestigated the role of Derlin-3 in retrotranslocation of ricin from the ER to thecytosol by performing overexpression and RNA interference (RNAi) studies.