Zhang Fan, Sun Shan, Feng Du, Zhao Wen-Long, Sui Sen-Fang
Department of Biological Sciences and Biotechnology, State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University, Beijing, China.
Traffic. 2009 Apr;10(4):411-24. doi: 10.1111/j.1600-0854.2009.00879.x. Epub 2009 Jan 24.
Toxins penetrate mammalian cells through various means. In this study, we report a unique strategy used by trichosanthin (TCS), a plant toxin with ribosome-inactivating activity, to penetrate host cells. We found that in both JAR and K562 cells, endocytosed TCS is incorporated into intraluminal vesicles of the multivesicular body (MVB) and is then secreted in association with these vesicles upon fusion of the MVB with the plasma membrane. The secreted TCS-loaded vesicles secreted by K562 cells move throughout the intercellular space and target syngeneic and specific allogeneic cells. Subsequent internalization permits delivery of the toxin into the cytosol, resulting in ribosomal inactivation and cell death. Thus, our findings provide a novel mechanism by which foreign proteins pass between and penetrate into mammalian cells.
毒素通过多种方式穿透哺乳动物细胞。在本研究中，我们报告了天花粉蛋白（TCS）——一种具有核糖体失活活性的植物毒素——用于穿透宿主细胞的独特策略。我们发现，在JAR和K562细胞中，内吞的TCS被纳入多泡体（MVB）的腔内小泡，然后在MVB与质膜融合时与这些小泡一起分泌。K562细胞分泌的携带TCS的小泡在整个细胞间空间移动，并靶向同基因和特定的异基因细胞。随后的内化使得毒素能够递送至细胞质溶胶，导致核糖体失活和细胞死亡。因此，我们的发现提供了一种外来蛋白质在哺乳动物细胞之间传递并穿透细胞的新机制。
