title: Enterohaemorrhagic Escherichia coli inhibits recycling endosome function and trafficking of surface receptors.
abstract: Enteropathogenic and enterohaemorrhagic Escherichia coli (EPEC/EHEC) manipulate many cell processes by injecting effector proteins from the bacteria into the host cell via a Type III secretion system. In this paper we report that the effector protein EspG disrupts recycling endosome function. In particular, we found that following transferrin binding and endocytosis EspG reduces recycling of the transferrin receptor (TfR), the prototypical recycling protein, from an intracellular location to the cell surface, resulting in an accumulation of TfR within the cell. The surface levels of three receptors [TfR, epidermal growth factor receptor (EGFR) and β1 integrin] were tested and found to be reduced dependent on EspG translocation. Furthermore, disruption of recycling endosome function and the reduced surface presentation of receptors was dependent on the previously reported RabGAP activity and ARF binding ability of EspG. This paper therefore supports the previous hypothesis that EspG acts as an enzyme scaffold perturbing cell signalling events, in this case altering recycling endosome function and cell surface receptor levels during infection.
authors.affiliation: MRC Centre for Molecular Bacteriology and Infection, Department of Life Sciences, Imperial College, London, UK.
authors.forename: Abigail
authors.initials: A
authors.lastname: Clements
authors.forename: Charlotte A
authors.initials: CA
authors.lastname: Stoneham
authors.forename: R Christopher D
authors.initials: RC
authors.lastname: Furniss
authors.forename: Gad
authors.initials: G
authors.lastname: Frankel
mesh_terms: D020823:ADP-Ribosylation Factor 1 / Q000378:metabolism; D011992:Endosomes / Q000187:drug effects* / Q000378:metabolism*; D054324:Enterohemorrhagic Escherichia coli / Q000502:physiology*; D066246:ErbB Receptors / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000378:metabolism; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D011485:Protein Binding; D011990:Receptors, Transferrin / Q000378:metabolism*
chemical_list: D029968:Escherichia coli Proteins; C429282:EspG protein, E coli; D020690:GTPase-Activating Proteins; D019012:Integrin beta1; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C119053:RABGAP1 protein, human; D011990:Receptors, Transferrin; C512478:EGFR protein, human; D066246:ErbB Receptors; D020823:ADP-Ribosylation Factor 1