Simpson J C, Roberts L M, Lord J M
Department of Biological Sciences, University of Warwick, Coventry, CV4 7AL, United Kingdom.
Exp Cell Res. 1996 Dec 15;229(2):447-51. doi: 10.1006/excr.1996.0390.
During the intoxication of mammalian cells by ricin, the catalytically active A chain must cross the membrane of an intracellular compartment in order to reach its ribosomal substrates in the cytosol. The actual site of ricin A chain translocation is unclear, and conflicting views hold that it enters the cytosol from endosomes or from an early compartment of the secretory pathway, possibly the lumen of the endoplasmic reticulum. Here we show that treating cells with brefeldin A, or transiently overexpressing mutant GTPases known to inhibit biochemical complexes mediating anterograde and retrograde transport between the endoplasmic reticulum and the Golgi complex, protected cells from intoxication by free ricin A chain. These data indicate that ricin A chain, either free or as part of intact ricin, reaches an early compartment of the secretory pathway before translocation into the cytosol occurs.
在蓖麻毒素使哺乳动物细胞中毒的过程中，具有催化活性的A链必须穿过细胞内区室的膜，才能到达胞质溶胶中的核糖体底物。蓖麻毒素A链转运的实际位点尚不清楚，存在相互矛盾的观点，认为它从内体或分泌途径的早期区室（可能是内质网腔）进入胞质溶胶。在这里，我们表明，用布雷菲德菌素A处理细胞，或瞬时过表达已知可抑制介导内质网和高尔基体复合体之间顺行和逆行转运的生化复合体的突变GTP酶，可保护细胞免受游离蓖麻毒素A链的中毒。这些数据表明，游离的或作为完整蓖麻毒素一部分的蓖麻毒素A链，在转运到胞质溶胶之前会到达分泌途径的早期区室。
