title: 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.
authors.affiliation: Unité des Interactions Bactéries-Cellules, INSERM U604, Institut Pasteur, 75015 Paris Cedex 15, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Seveau
authors.forename: Hélène
authors.initials: H
authors.lastname: Bierne
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Giroux
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Prévost
authors.forename: Pascale
authors.initials: P
authors.lastname: Cossart
mesh_terms: D000199:Actins / Q000096:biosynthesis; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism*; D002460:Cell Line; D002522:Chlorocebus aethiops; D002784:Cholesterol / Q000172:deficiency; D003505:Cyclodextrins / Q000494:pharmacology; D005677:G(M1) Ganglioside / Q000378:metabolism; D017261:Glycosylphosphatidylinositols; D006790:Host-Parasite Interactions / Q000502:physiology*; D006801:Humans; D008089:Listeria monocytogenes / Q000378:metabolism* / Q000648:ultrastructure; D008088:Listeriosis / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008855:Microscopy, Electron, Scanning; D019814:Myristic Acid / Q000378:metabolism; D019308:Palmitic Acid / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D020239:Receptor Cross-Talk / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D047392:beta-Cyclodextrins
chemical_list: D000199:Actins; D001426:Bacterial Proteins; D015820:Cadherins; D002784:Cholesterol; D003505:Cyclodextrins; D005677:G(M1) Ganglioside; D017261:Glycosylphosphatidylinositols; D008565:Membrane Proteins; D019814:Myristic Acid; D019308:Palmitic Acid; D019869:Phosphatidylinositol 3-Kinases; D019859:Proto-Oncogene Proteins c-met; D047392:beta-Cyclodextrins; C095768:inlB protein, Listeria monocytogenes; C108732:methyl-beta-cyclodextrin; C081751:plasmanylinositol glycan; C069761:internalin protein, Bacteria