InlB-invasion Pathway

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[Pizarro-Cerda et al., Cold Spring Harbor Perspectives in Medecine 2012]

Signaling cascades activated via the InlB-invasion pathways. Interaction of InlA and/or InlB with their respective host-cell surface receptors E-cadherin and Met induces ubiquitination of the receptors by the ubiquitin ligases Hakai in the case of E-cadherin or Cbl in the case of Met and subsequent recruitment of the clathrin endocytosis machinery (Dab2, clathrin, dynamin, Hip1R, MyoVI), which provides an initial platform for actin cytoskeleton polymerization. Downstream from E-cadherin, this first actin polymerization wave is activated by Src and cortactin, which promote recruitment of the Arp2/3 complex; association of β/α-catenins to the bacterial entry sites favors dynamic interactions between the E-cadherin cytoplasmic tail and the actin cytoskeleton. In the case of Met, actin polymerization can be first coordinated by dynamin and cortactin upstream of the Arp2/3 complex, and subsequently by a signaling cascade downstream from the type IA PI 3-kinase, which involves the small GTPases Rac1 and Cdc42, abi1, WAVE, and N-WASP (depending on the cell type); LIM-K and cofilin play a critical role in the depolymerization of actin to allow completion of the bacterial internalization process.

 

 

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[Pizarro-Cerda et al., Journal of Pathology 2006]

The InlB-invasion pathway. (A) Schematic model of the molecules implicated in the InlB-invasion pathway.

Membrane-bound InlB or released InlB interacts with its receptor, the hepatocyte growth factor receptor Met: this interaction leads to dimerization (not shown) and autophosphorylation of Met, which recruits the adaptor molecules Shc, Gab1, and Cbl to the bacterial entry site. These adaptors help to recruit phosphatidylinositol 3-kinase (PI3K) type I to the plasma membrane, inducing the formation of phosphatidylinositol 3,4,5-triphosphate and activation of the small GTP-binding protein Rac, both upstream of the cytoskeletal rearrangements required for bacterial entry. Cbl is also a ubiquitin ligase that induces the clathrin-dependent internalization of Met, favouring bacterial internalization. (B) Immunofluorescence showing the recruitment of clathrin (red) at the

bacterial entry site (intracellular bacteria, green; extracellular bacteria, blue; overlay of clathrin and intracellular bacteria, yellow). (C) Three-dimensional reconstitution of the recruitment of clathrin by L. monocytogenes (colours similar to those in B)

 

 

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[Photo:H.Bierne, UIBC Institut Pasteur]

Recruitment of the Arp2/3 complex to InlB-beads (a-c) or bacteria (d-f) – induced phagocytic cups. Cells were stained with FITC-phalloidin (green) and anti-Arp3 Ab (red). The bacterium is labeled with anti-InlA Ab (in blue, f). Images represent confocal slices of 0.6 mm (beads) and 1.2 mm (bacteria). Scale bars, 2mm.

 

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[Braun et al., Molecular Microbiology 1998]

The InlB-invasion pathway. a) Schematic model of the molecules implicated in the InlB-invasion pathway.

Membrane-bound InlB or released InlB interacts with its receptor, the hepatocyte growth factor receptor Met: this interaction leads to dimerization (not shown) and autophosphorylation of Met, which recruits the adaptor molecules Shc, Gab1, and Cbl to the bacterial entry site. These adaptors help to recruit phosphatidylinositol 3-kinase (PI3K) type I to the plasma membrane, inducing the formation of phosphatidylinositol 3,4,5-triphosphate and activation of the small GTP-binding protein Rac, both upstream of the cytoskeletal rearrangements required for bacterial entry. Cbl is also a ubiquitin ligase that induces the clathrin-dependent internalization of Met, favouring bacterial internalization. b) Immunofluorescence showing the recruitment of clathrin (red) at the bacterial entry site (intracellular bacteria, green; extracellular bacteria, blue; overlay of clathrin and intracellular bacteria, yellow). c) Three-dimensional reconstitution of the recruitment of clathrin by L. monocytogenes (colours similar to those in b).

Updated on 13/05/2014

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Lab address

Unité Interactions Bactéries-Cellules

INSERM U604 INRA USC2020
Institut Pasteur
25, Rue du Docteur Roux
75724 Paris Cedex 15 FRANCE

 

Phone: + 33 (1) 45 68 88 41

Secretary: + 33 (1) 40 61 30 32

Fax: + 33 (1) 45 68 87 06

 

Our laboratory is located on the ground floor at the 53C entrance of the Roux Building (25, rue du Docteur Roux)

The metro stations Pasteur (line 6) and Volontaires (line 12) are within a 5 min walking distance from the Pasteur Institute.

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