2006/02/02 by Monika Słomińska-Wojewódzka, Tone F. Gregers, Sébastien Wälchli +1 · 78 citations
Biochemistry, Genetics and Molecular Biology · Immunology and Microbiology · #Biochemistry #Biology #Cell biology #Cytosol #Endoplasmic reticulum #Enzyme #Galectins and Cancer Biology #Ricin #Toxin #Toxin Mechanisms and Immunotoxins #Transgenic Plants and Applications
paper · open access · doi:10.1091/mbc.e05-10-0961
published in Molecular Biology of the Cell 17(4), 1664-1675 (American Society for Cell Biology)
openalex publication_date 2006/02/02 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/22
The plant toxin ricin is transported retrogradely from the cell surface to the endoplasmic reticulum (ER) from where the enzymatically active part is retrotranslocated to the cytosol, presumably by the same mechanism as used by misfolded proteins. The ER degradation enhancing alpha-mannosidase I-like protein, EDEM, is responsible for directing aberrant proteins for ER-associated protein degradation. In this study, we have investigated whether EDEM is involved in ricin retrotranslocation. Overexpression of EDEM strongly protects against ricin. However, when the interaction between EDEM and misfolded proteins is inhibited by kifunensin, EDEM promotes retrotranslocation of ricin from the ER to the cytosol. Furthermore, puromycin, which inhibits synthesis and thereby transport of proteins into the ER, counteracted the protection seen in EDEM-transfected cells. Coimmunoprecipitation studies revealed that ricin can interact with EDEM and with Sec61alpha, and both kifunensin and puromycin increase these interactions. Importantly, vector-based RNA interference against EDEM, which leads to reduction of the cellular level of EDEM, decreased retrotranslocation of ricin A-chain to the cytosol. In conclusion, our results indicate that EDEM is involved in retrotranslocation of ricin from the ER to the cytosol.