title: Enteropathogenic Escherichia coli recruits the cellular inositol phosphatase SHIP2 to regulate actin-pedestal formation.
abstract: Adhesion of enteropathogenic Escherichia coli to epithelial cells triggers actin-rich pedestal formation beneath the bacteria. Pedestal formation requires delivery and insertion of the bacterial translocated intimin receptor (Tir) into the host plasma membrane. The C-terminal regions in Tir, encompassing Y483 and Y511, share sequence similarity with cellular immunoreceptor tyrosine-based inhibition motifs (ITIMs), which are critical regulators of eukaryotic signaling pathways. We demonstrate that Y483 and Y511 within tandem ITIM-like sequences are essential for recruiting SHIP2, a host inositol phosphatase. SHIP2 controls condensed F-actin-pedestal formation by engaging the adaptor SHC and by generating a PI(3,4)P(2)-enriched lipid platform for recruitment of the cytoskeletal regulator lamellipodin. Therefore, mimicry of eukaryotic receptor motifs by Tir controls both the lipid and protein composition of the signaling platform necessary for pedestal formation. Further, the dual action of SHIP2's scaffolding and phosphatase functions ensures tight compartmentalization and coordination of actin dynamics during pedestal formation.
authors.affiliation: University of Cambridge, Department of Pathology, Tennis Court Road, Cambridge CB21QP, UK.
authors.forename: Katherine
authors.initials: K
authors.lastname: Smith
authors.forename: Daniel
authors.initials: D
authors.lastname: Humphreys
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Hume
authors.forename: Vassilis
authors.initials: V
authors.lastname: Koronakis
mesh_terms: D000199:Actins / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D054308:Enteropathogenic Escherichia coli / Q000472:pathogenicity*; D004847:Epithelial Cells / Q000382:microbiology*; D029968:Escherichia coli Proteins / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010716:Phosphatidylinositols / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000502:physiology*; D055765:Shc Signaling Adaptor Proteins / Q000378:metabolism; D015398:Signal Transduction; D037521:Virulence Factors / Q000502:physiology*
chemical_list: D000199:Actins; D002352:Carrier Proteins; D029968:Escherichia coli Proteins; D008565:Membrane Proteins; D010716:Phosphatidylinositols; C493339:RAPH1 protein, human; D011956:Receptors, Cell Surface; D055765:Shc Signaling Adaptor Proteins; C109287:Tir protein, E coli; D037521:Virulence Factors; D010744:Phosphoric Monoester Hydrolases; C098706:INPPL1 protein, human; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases