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Role of lipid rafts in E-cadherin- and HGF-R/met-mediated entry of Listeria monocytogenes into host cells

Abstract : Listeria monocytogenes uptake by nonphagocytic cells is promoted by the bacterial invasion proteins internalin and InlB, which bind to their host receptors E-cadherin and hepatocyte growth factor receptor (HGF-R)/Met, respectively. Here, we present evidence that plasma membrane organization in lipid domains is critical for Listeria uptake. Cholesterol depletion by methyl-beta-cyclodextrin reversibly inhibited Listeria entry. Lipid raft markers, such as glycosylphosphatidylinositol-linked proteins, a myristoylated and palmitoylated peptide and the ganglioside GM1 were recruited at the bacterial entry site. We analyzed which molecular events require membrane cholesterol and found that the presence of E-cadherin in lipid domains was necessary for initial interaction with internalin to promote bacterial entry. In contrast, the initial interaction of InlB with HGF-R did not require membrane cholesterol, whereas downstream signaling leading to F-actin polymerization was cholesterol dependent. Our work, in addition to documenting for the first time the role of lipid rafts in Listeria entry, provides the first evidence that E-cadherin and HGF-R require lipid domain integrity for their full activity.
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Stéphanie Seveau, Hélène Bierne, Stéphanie Giroux, Marie-Christine Prévost, Pascale Cossart. Role of lipid rafts in E-cadherin- and HGF-R/met-mediated entry of Listeria monocytogenes into host cells. Journal of Cell Biology, Rockefeller University Press, 2004, 166 (5), pp.743-753. ⟨10.1083/jcb.200406078⟩. ⟨hal-02679649⟩

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