Mechanistic insight into A/B toxin cell entry via ubiquitin-mediated receptor endocytosis

微生物、植物和病毒A/B毒素如霍乱和志贺毒素、蓖麻毒素和病毒A/B毒素K28通过受体介导的内吞作用和分泌途径（通过早期核内体、高尔基体和内质网）的逆行转运进入真核靶细胞，然后逆行转运到细胞质中，最终杀死相应的宿主。虽然大多数这些过程和所涉及的细胞成分仍然知之甚少，但本项目旨在解决和剖析中毒的初始步骤，即通过泛素介导的受体内吞作用摄取A/B毒素并随后进入内吞途径。由于一些A/B毒素可以通过不同的策略进入和穿透真核细胞，对酵母中病毒A/B毒素货物（K28）泛素介导的内吞作用的详细分析可能会揭示非规范的内吞进入途径，并扩展我们目前对医学相关A/B毒素的内吞作用和细胞内运输的了解。

Microbial, plant and viral A/B toxins such as cholera and Shiga toxin, ricin and the viral A/B toxin K28 enter eukaryotic target cells by receptor-mediated endocytosis and retrograde transport through the secretory pathway (via early endosomes, Golgi and ER) before being retrotranslocated into the cytosol to finally kill their corresponding host. While most of these processes and cellular components involved are still poorly understood, the present project intends to address and dissect the initial step of intoxification which is A/B toxin uptake via ubiquitin-mediated receptor endocytosis and subsequent sorting into the endocytic pathway. Since some A/B toxins can use different strategies to enter and penetrate eukaryotic cells, detailed analysis of ubiquitin-mediated endocytosis of a viral A/B toxin cargo (K28) in yeast will possibly reveal non-canonical endocytic entry routes and extend our current knowledge of endocytosis and intracellular trafficking of medically relevant A/B toxins.