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

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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.