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Pet, a Non-AB Toxin, Is Transported and Translocated into Epithelial Cells by a Retrograde Trafficking Pathway

Department of Cell Biology, Centro de Investigación y de Estudios Avanzados (Cinvestav-Zacatenco), Ap. Postal 14-740, 07000 México, DF, Mexico,¹ Biomolecular Science Center and Department of Molecular Biology and Microbiology, University of Central Florida, 12722 Research Parkway, Orlando, Florida 32826²

Received 20 September 2006/ Returned for modification 9 November 2006/ Accepted 5 February 2007

The plasmid-encoded toxin (Pet) of enteroaggregative Escherichia coli is a 104-kDa autotransporter protein that exhibits proteolytic activity against the actin-binding protein -fodrin. Intracellular cleavage of epithelial fodrin by Pet disrupts the actin cytoskeleton, causing both cytotoxic and enterotoxic effects. Intoxication requires the serine protease activity of Pet and toxin endocytosis from clathrin-coated pits. The additional events in the intracellular trafficking of Pet are largely uncharacterized. Here, we determined by confocal microscopy that internalized Pet is transferred from the early endosomes to the Golgi apparatus and then travels to the endoplasmic reticulum (ER). Pet associates with the Sec61p translocon before it moves into the cytosol as an intact, 104-kDa protein. This translocation process contrasts with the export of other ER-translocating toxins, in which only the catalytic A subunit of the AB toxin enters the cytosol. However, like intoxication with these AB toxins, Pet intoxication was inhibited in a subset of mutant CHO cell lines with aberrant activity in the ER-associated degradation pathway of ER-to-cytosol translocation. This is the first report which documents the cell surface-to-ER and ER-to-cytosol trafficking of a bacterial non-AB toxin.

Published ahead of print on 12 February 2007.

Editor: A. D. O'Brien

This article has been cited by other articles:

• Navarro-Garcia, F., Canizalez-Roman, A., Vidal, J. E., Salazar, Ma. I. (2007). Intoxication of epithelial cells by plasmid-encoded toxin requires clathrin-mediated endocytosis. Microbiology 153: 2828-2838 [Abstract] [Full Text]