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

微生物、植物和病毒A/B毒素如霍乱和滋贺毒素、蓖麻毒蛋白和病毒A/B毒素K28通过受体介导的内吞作用进入真核靶细胞，并通过分泌途径（通过早期内体、高尔基体和ER）逆行转运，然后被逆转运到胞质溶胶中，最终杀死它们相应的宿主。虽然大多数这些过程和涉及的细胞成分仍然知之甚少，本项目旨在解决和剖析的初始步骤inphilification，这是A/B毒素摄取通过泛素介导的受体内吞作用和随后的排序到内吞途径。由于一些A/B毒素可以使用不同的策略进入并穿透真核细胞，因此对酵母中病毒A/B毒素货物（K28）的泛素介导的内吞作用的详细分析可能会揭示非典型的内吞进入途径，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知识。

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.