eeyarestatin 1 interferes with both retrograde and anterograde intracellular trafficking pathwayseeyarestatin 1干扰顺行和逆行性细胞内走私通道.pdfVIP

Eeyarestatin 1 Interferes with Both Retrograde and Anterograde Intracellular Trafficking Pathways 1 2¤a 3 1¤b 1 Mina-Olga Aletrari , Craig McKibbin , Helen Williams , Vidya Pawar , Paola Pietroni , J. Michael 1 3,4 3 2 2 1 Lord , Sabine L. Flitsch , Roger Whitehead , Eileithyia Swanton , Stephen High *, Robert A. Spooner * 1 School of Life Sciences, University of Warwick, Coventry, United Kingdom, 2 Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom, 3 School of Chemistry, University of Manchester, Manchester, United Kingdom, 4 Manchester Interdisciplinary Biocentre, University of Manchester, Manchester, United Kingdom Abstract Background: The small molecule Eeyarestatin I (ESI) inhibits the endoplasmic reticulum (ER)-cytosol dislocation and subsequent degradation of ERAD (ER associated protein degradation) substrates. Toxins such as ricin and Shiga/Shiga-like toxins (SLTx) are endocytosed and trafficked to the ER. Their catalytic subunits are thought to utilise ERAD-like mechanisms to dislocate from the ER into the cytosol, where a proportion uncouples from the ERAD process, recovers a catalytic conformation and destroys their cellular targets. We therefore investigated ESI as a potential inhibitor of toxin dislocation. Methodology and Principal Findings: Using cytotoxicity measurements, we found no role for ES as an inhibitor of toxin I dislo