title: Eps15 and Epsin1 are crucial for enteropathogenic Escherichia coli pedestal formation despite the absence of adaptor protein 2.
abstract: Enteropathogenic Escherichia coli (EPEC) are primarily extracellular pathogens that generate actin-rich structures known as pedestals during their pathogenesis. Surprising evidence has demonstrated that despite maintaining an extracellular location, EPEC require the endocytic protein, clathrin, for pedestal formation. To evaluate the strategies EPEC use to usurp endocytic machinery, we investigated the roles of a number of clathrin-coated pits components, adaptor protein 2 (AP-2), Eps15 and epsin1, during EPEC infections. We demonstrated that in conjunction with clathrin, pedestal formation also required the recruitment of Eps15 and epsin1 but not AP-2. Because AP-2 orchestrates the recruitment of clathrin, Eps15, and epsin1, as well as other adaptors, during assembly of clathrin-coated pits at the plasma membrane, our findings reveal a novel internalization subversion strategy employed by EPEC. These results further emphasize the recent paradigm that endocytic proteins are important for EPEC-mediated disease.
authors.affiliation: Department of Biological Sciences, Simon Fraser University, Burnaby, British Columbia, Canada.
authors.forename: Ann E
authors.initials: AE
authors.lastname: Lin
authors.forename: Alexandre
authors.initials: A
authors.lastname: Benmerah
authors.forename: Julian A
authors.initials: JA
authors.lastname: Guttman
mesh_terms: D033962:Adaptor Protein Complex 2 / Q000378:metabolism / Q000502:physiology*; D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism / Q000502:physiology*; D001422:Bacterial Adhesion / Q000502:physiology; D058947:Bacterial Secretion Systems / Q000502:physiology; D018938:Caco-2 Cells / Q000382:microbiology; D002135:Calcium-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D002966:Clathrin / Q000378:metabolism / Q000502:physiology; D004705:Endocytosis; D054308:Enteropathogenic Escherichia coli / Q000378:metabolism*; D004927:Escherichia coli Infections / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000378:metabolism / Q000502:physiology; D006367:HeLa Cells / Q000382:microbiology; D054884:Host-Pathogen Interactions; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism / Q000502:physiology*; D008856:Microscopy, Fluorescence; D010750:Phosphoproteins / Q000378:metabolism / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000378:metabolism / Q000502:physiology
chemical_list: D033962:Adaptor Protein Complex 2; D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D058947:Bacterial Secretion Systems; D002135:Calcium-Binding Proteins; D002966:Clathrin; C486206:EPS15 protein, human; D029968:Escherichia coli Proteins; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D011956:Receptors, Cell Surface; C109287:Tir protein, E coli; C114154:epsin