Signal transduction between enteropathogenic Escherichia coli (EPEC) and epithelial cells: EPEC induces tyrosine phosphorylation of host cell proteins to initiate cytoskeletal rearrangement and bacterial uptake

Rosenshine, Ilan; Donnenberg, Michael S.; Kaper, James B.; Finlay, B. Brett

doi:10.1016/0962-8924(92)90046-p

Cited by 87 publications

(165 citation statements)

References 24 publications

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“…Analysis of the Tir sequence predicts two transmembrane domains (TMDs), which suggests a hairpin-like structure, with the region between the TMDs forming a loop exposed to the extracellular space and the N-and C-terminal regions (with four of the tyrosines) in the host cell cytosol. This model is supported by the fact that Tir is labelled with anti-phosphotyrosine antibodies in infected cells only when they are permeabilized (Rosenshine et al, 1992). Also, Tir proteins tagged at the N-and C-termini are only labelled in permeabilized cells (unpublished observations).…”

Section: Introductionmentioning

confidence: 79%

“…4B, the higher molecular weight bands observed in the membrane fractions corresponded to the tyrosine-phosphorylated forms of Tir. In the insoluble fractions, a 70 kDa band is observed in all bacteria-infected samples, corresponding to a tyrosinephosphorylated EPEC protein (Rosenshine et al, 1992). Phosphorylated Tir and Tir-9, -10 and -12 were detected in the membrane fraction, suggesting that this phosphorylation is dependent on translocation to the HeLa cell membrane and that the IBD is not needed for Tir translocation.…”

Section: The Intimin-binding Domain Is Not Involved In Tir Translocatmentioning

confidence: 93%

“…Initially, bacteria adhere to the cell membrane in microcolonies by a process called localized adherence, mediated by the plasmidencoded bundle-forming pilus (BFP) (Giron et al, 1991). In the second step, there is effacement of the microvilli, and several signal transduction pathways are activated in the host cell, including release of IP3 and phosphorylation of proteins (Rosenshine et al, 1992;Foubister et al, 1994). During this stage, the bacteria translocate a protein called Tir (for translocated intimin receptor) to the mammalian cell membrane, where it acts as the receptor for EPEC's adhesion molecule intimin (Kenny et al, 1997a).…”

Section: Introductionmentioning

confidence: 99%

“…Intimin is a 94 kDa outer membrane protein encoded by eae (Jerse and Kaper, 1991) and is a member of the invasin/intimin-like protein family. Intimin mutants can activate some signalling in the host cell, inducing tyrosine phosphorylation of Tir and generalized actin accumulation, but they cannot focus actin into pedestal-like structures (Donnenberg and Kaper, 1991;Rosenshine et al, 1992;Donnenberg et al, 1993a). Intimin is required for A /E lesion formation and for complete virulence in humans and animals.…”

Section: Introductionmentioning

confidence: 99%

“…Tir has been shown to be an integral transmembrane protein in epithelial cells (Rosenshine et al, 1996b). After insertion in the host cell membrane, it is tyrosine phosphorylated (Rosenshine et al, 1992) at one or more of the six tyrosine residues contained in its sequence and undergoes an electrophoretic mobility shift to a molecular weight of 90 kDa. However, the role that Tir phosphorylation plays in infection remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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Identification of the intimin-binding domain of Tir of enteropathogenic Escherichia coli

et al. 1999

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SummaryEnteropathogenic Escherichia coli (EPEC) attaches intimately to mammalian cells via a bacterial outer membrane adhesion molecule, intimin, and its receptor in the host cell membrane, Tir. Tir is a bacterial protein translocated into the host cell membrane and tyrosine phosphorylated after insertion. Tir±inti-min binding induces organized actin polymerization beneath the adherent bacteria, resulting in the formation of pedestal-like structures. A series of Tir deletion derivatives were constructed to analyse which Tir domains are involved in intimin binding. We have localized the intimin-binding domain (IBD) of Tir using a yeast two-hybrid system and a gel-overlay approach to a region of 109 amino acids that is predicted to be exposed on the surface of the plasma membrane. A truncated Tir protein lacking this domain was translocated to the host cell membrane and tyrosine phosphorylated, but failed to bind intimin or to induce either actin polymerization or Tir accumulation beneath the bacteria. These results indicate that only a small region of Tir is needed to bind intimin and support the predicted topology for Tir, with both N-and C-terminal regions in the mammalian cell cytosol. They also con®rm that Tir±intimin interactions are needed for cytoskeletal organization. We have also identi®ed N-terminal regions involved in Tir stability and Tir secretion to the media.

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Section: Introductionmentioning

confidence: 79%

Section: The Intimin-binding Domain Is Not Involved In Tir Translocatmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Identification of the intimin-binding domain of Tir of enteropathogenic Escherichia coli

et al. 1999

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Cyclophilin A ControlsSalmonellaInternalization Levels and is Present atE. coliActin‐Rich Pedestals

Dhanda

Warren

Chiu

et al. 2018

The Anatomical Record

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Salmonella enterica serovar Typhimurium (S. Typhimurium), enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) commandeer the actin cytoskeleton of their host cells as a crucial step in their infectious processes. These pathogens depend on the injection of their own effectors directly into target host cells in order to usurp cellular signaling pathways that lead to morphological actin rearrangements in those cells. Here we show that the PPIase Cyclophilin A (CypA) is a novel component of S. Typhimurium‐induced membrane ruffles and functions to restrict bacterial invasion levels, as in cells depleted of CypA, bacterial loads increase. We also demonstrate that CypA requires the EPEC effector Tir as well as pedestal formation for its recruitment to bacterial attachment sites and that its presence at pedestals also holds during EHEC infections. Finally, we demonstrate that CypA is found at lamellipodia; actin‐rich structures at the leading edge of motile cells. Our findings further establish CypA as a component of dynamic actin‐rich structures formed during bacterial infections and within cells in general. Anat Rec, 301:2086–2094, 2018. © 2018 Wiley Periodicals, Inc.

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Distribution of PDLIM1 at actin‐rich structures generated by invasive and adherent bacterial pathogens

Dhanda

Yang

Kooner

et al. 2020

The Anatomical Record

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The enteric bacterial pathogens Listeria monocytogenes (Listeria) and enteropathogenic Escherichia coli (EPEC) remodel the eukaryotic actin cytoskeleton during their disease processes. Listeria generate slender actin‐rich comet/rocket tails to move intracellularly, and later, finger‐like membrane protrusions to spread amongst host cells. EPEC remain extracellular, but generate similar actin‐rich membranous protrusions (termed pedestals) to move atop the host epithelia. These structures are crucial for disease as diarrheal (and systemic) infections are significantly abrogated during infections with mutant strains that are unable to generate the structures. The current repertoire of host components enriched within these structures is vast and diverse. In this protein catalog, we and others have found that host actin crosslinkers, such as palladin and α‐actinin‐1, are routinely exploited. To expand on this list, we set out to investigate the distribution of PDLIM1, a scaffolding protein and binding partner of palladin and α‐actinin‐1, during bacterial infections. We show that PDLIM1 localizes to the site of initial Listeria entry into cells. Following this, PDLIM1 localizes to actin filament clouds surrounding immotile bacteria, and then colocalizes with actin once the comet/rocket tails are generated. Unlike palladin or α‐actinin‐1, PDLIM1 is maintained within the actin‐rich core of membrane protrusions. Conversely, α‐actinin‐1, but not PDLIM1 (or palladin), is enriched at the membrane invagination that internalizes the Listeria‐containing membrane protrusion. We also show that PDLIM1 is a component of the EPEC pedestal core and that its recruitment is dependent on the bacterial effector Tir. Our findings highlight PDLIM1 as another protein present within pathogen‐induced actin‐rich structures.

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Signal transduction between enteropathogenic Escherichia coli (EPEC) and epithelial cells: EPEC induces tyrosine phosphorylation of host cell proteins to initiate cytoskeletal rearrangement and bacterial uptake

Cited by 87 publications

References 24 publications

Identification of the intimin-binding domain of Tir of enteropathogenic Escherichia coli

Identification of the intimin-binding domain of Tir of enteropathogenic Escherichia coli

Cyclophilin A ControlsSalmonellaInternalization Levels and is Present atE. coliActin‐Rich Pedestals

Distribution of PDLIM1 at actin‐rich structures generated by invasive and adherent bacterial pathogens

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