Proposed mechanism of ETX induced transcytosis.

(1) ETX binds to MAL and oligomerizes, (2) causing recruitment of CAV1. (3) Recruitment of CAV1 results in increased caveolae formation and internalization and is dependent on dynamin. (4) Internalized caveolae, containing various blood-borne material, rapidly fuse with EEA1+ early endosomes, which traffic contents to RAB7+ late endosomes, (5) ultimately forming MVB. We propose that MVB then fuse with the basal membrane of the endothelial cells, releasing their contents into the brain parenchyma.