Title

Pet, a non-AB toxin, is transported and translocated into epithelial cells by a retrograde trafficking pathway

Authors

Authors

F. Navarro-Garcia; A. Canizalez-Roman; K. E. Burlingame; K. Teter;J. E. Vidal

Comments

Authors: contact us about adding a copy of your work at STARS@ucf.edu

Abbreviated Journal Title

Infect. Immun.

Keywords

ENTEROAGGREGATIVE ESCHERICHIA-COLI; TRANS-GOLGI NETWORK; PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY; ENDOPLASMIC-RETICULUM; DIPHTHERIA-TOXIN; CHOLERA-TOXIN; BREFELDIN-A; INTRACELLULAR TRAFFICKING; AUTOTRANSPORTER PROTEINS; WORTMANNIN ALTERS; Immunology; Infectious Diseases

Abstract

The plasmid-encoded toxin (Pet) of enteroaggregative Escherichia coli is a 104-kDa autotransporter protein that exhibits proteolytic activity against the actin-binding protein alpha-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.

Journal Title

Infection and Immunity

Volume

75

Issue/Number

5

Publication Date

1-1-2007

Document Type

Article

Language

English

First Page

2101

Last Page

2109

WOS Identifier

WOS:000246345000002

ISSN

0019-9567

Share

COinS