InlA-mediated entry of Listeria monocytogenes into host cells

Stable Identifier
R-HSA-8876493
Type
Pathway
Species
Homo sapiens
Related Species
Listeria monocytogenes
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The pathogenic bacteria Listeria monocytogenes can enter host cells through endocytosis triggered by binding of the bacterial cell wall protein internalin (InlA) to the E-cadherin (CDH1) complex at the host cell plasma membrane (Mengaud et al. 1996, Lecuit et al. 1999). Binding of InlA to CDH1, similar to CDH1 engagement during normal cell-to-cell adhesion, triggers activation of the SRC protein tyrosine kinase and phosphorylation of CDH1 and CDH1-bound beta-catenin (CTNNB1) (Fujita et al. 2002, McLachlan et al. 2007, Sousa et al. 2007, Bonazzi et al. 2008). Integrins likely contribute to CDH1-triggered SRC activation, and ERKs (MAPK1 and MAPK3), ROCKs and MLCK may also be involved (Avizienyte et al. 2002, Avizienyte et al. 2004, Martinez-Rico et al. 2010). FAK1 (PTK2), a SRC-regulated protein tyrosine kinase, may contribute to SRC-mediated regulation of CDH1 (Avizienyte et al. 2002).
Phosphorylation of CDH1 and CTNNB1 by SRC creates docking sites for a CBL-like ubiquitin protein ligase Hakai (CBLL1). CBLL1 ubiquitinates SRC-phosphorylated CDH1 and CTNNB1 upon InlA binding, as well as in the context of CDH1-mediated cell-to-cell adhesion, thus triggering CDH1 endocytosis (Fujita et al. 2002, Bonazzi et al. 2008, Mukherjee et al. 2012).
CBLL1 may also undergo SRC-mediated phosphorylation and subsequent autoubiquitination (Fujita et al. 2002).
Both clathrin-mediated and caveolin-mediated endocytosis are implicated in the InlA-mediated entry of Listeria monocytogenes to host cells (Veiga et al. 2007). SRC-mediated phosphorylation of cortactin and the ARP2/3 complex involved in actin polymerization is implicated in CDH1 endocytosis and Listeria monocytogenes internalization (Sousa et al. 2007, Ren et al. 2009).

Literature References
PubMed ID Title Journal Year
20144995 Integrins stimulate E-cadherin-mediated intercellular adhesion by regulating Src-kinase activation and actomyosin contractility

Martinez-Rico, C, Pincet, F, Thiery, JP, Dufour, S

J. Cell. Sci. 2010
19457864 Cortactin is a functional target of E-cadherin-activated Src family kinases in MCF7 epithelial monolayers

Ren, G, Helwani, FM, Verma, S, McLachlan, RW, Weed, SA, Yap, AS

J. Biol. Chem. 2009
18624796 Successive post-translational modifications of E-cadherin are required for InlA-mediated internalization of Listeria monocytogenes

Bonazzi, M, Veiga, E, Pizarro-Cerdá, J, Cossart, P

Cell. Microbiol. 2008
10406800 A single amino acid in E-cadherin responsible for host specificity towards the human pathogen Listeria monocytogenes

Lecuit, M, Dramsi, S, Gottardi, C, Fedor-Chaiken, M, Gumbiner, B, Cossart, P

EMBO J. 1999
22252131 Structure of a novel phosphotyrosine-binding domain in Hakai that targets E-cadherin

Mukherjee, M, Chow, SY, Yusoff, P, Seetharaman, J, Ng, C, Sinniah, S, Koh, XW, Asgar, NF, Li, D, Yim, D, Jackson, RA, Yew, J, Qian, J, Iyu, A, Lim, YP, Zhou, X, Sze, SK, Guy, GR, Sivaraman, J

EMBO J. 2012
17553930 E-cadherin adhesion activates c-Src signaling at cell-cell contacts

McLachlan, RW, Kraemer, A, Helwani, FM, Kovacs, EM, Yap, AS

Mol. Biol. Cell 2007
8601315 E-cadherin is the receptor for internalin, a surface protein required for entry of L. monocytogenes into epithelial cells

Mengaud, J, Ohayon, H, Gounon, P, Mege R-M, R-M, Cossart, P

Cell 1996
15075377 Src SH3/2 domain-mediated peripheral accumulation of Src and phospho-myosin is linked to deregulation of E-cadherin and the epithelial-mesenchymal transition

Avizienyte, E, Fincham, VJ, Brunton, VG, Frame, MC

Mol. Biol. Cell 2004
11836526 Hakai, a c-Cbl-like protein, ubiquitinates and induces endocytosis of the E-cadherin complex

Fujita, Y, Krause, G, Scheffner, M, Zechner, D, Leddy, HE, Behrens, J, Sommer, T, Birchmeier, W

Nat. Cell Biol. 2002
12134161 Src-induced de-regulation of E-cadherin in colon cancer cells requires integrin signalling

Avizienyte, E, Wyke, AW, Jones, RJ, McLean, GW, Westhoff, MA, Brunton, VG, Frame, MC

Nat. Cell Biol. 2002
17627624 Src, cortactin and Arp2/3 complex are required for E-cadherin-mediated internalization of Listeria into cells

Sousa, S, Cabanes, D, Bougnères, L, Lecuit, M, Sansonetti, P, Tran-Van-Nhieu, G, Cossart, P

Cell. Microbiol. 2007
18005755 Invasive and adherent bacterial pathogens co-Opt host clathrin for infection

Veiga, E, Guttman, JA, Bonazzi, M, Boucrot, E, Toledo-Arana, A, Lin, AE, Enninga, J, Pizarro-Cerdá, J, Finlay, BB, Kirchhausen, T, Cossart, P

Cell Host Microbe 2007
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Event Information
Disease
Name Identifier Synonyms
listeriosis 11573 Infection by Listeria monocytogenes, Infection due to Listeria monocytogenes, Listeria infection, Listeriosis
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