Tight junctions and enteropathogenic E. coli.
Enteropathogenic E. coli (EPEC) are a leading cause of infantile diarrhea in developing countries, resulting in millions of deaths each year. EPEC secrete virulence factors, also called effectors, directly into host intestinal epithelial cells via type three secretion systems. Secreted effectors then affect host signaling pathways to induce several phenotypes, which ultimately lead to disease. Among the over 20 secreted effectors is E. coli secreted protein F (EspF), a 206 amino acid protein believed to be central to EPEC pathogenesis, as it disrupts tight junction structure and function. Although the mechanism by which this occurs is unknown, EspF has recently been found to contain several protein-protein interaction domains that may be involved. We have shown EspF to interact with the endocytic regulators sorting nexin 9 (SNX9) and N-WASP via non-exclusive binding sites. These interactions induce actin polymerization in vitro, and interaction with SNX9 alters its endocytic activity, as EspF induces the formation of tubular vesicles in a manner dependent upon its interaction with SNX9. EspF, therefore, appears to hijack endocytic regulation via SNX9 and possibly N-WASP interaction, to affect an as yet unidentified pathogenic phenotype.
Weflen
Andrew W
AW
Department of Medicine, Section of Digestive Diseases and Nutrition, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
Alto
Neal M
NM
Hecht
Gail A
GA
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism; D054308:Enteropathogenic Escherichia coli / Q000378:metabolism* / Q000472:pathogenicity; D029968:Escherichia coli Proteins / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D019108:Tight Junctions / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000378:metabolism; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal / Q000378:metabolism
D002352:Carrier Proteins; D029968:Escherichia coli Proteins; C489109:EspFU protein, E coli; D047908:Intracellular Signaling Peptides and Proteins; D033921:Vesicular Transport Proteins; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal