title: A common clathrin-mediated machinery co-ordinates cell-cell adhesion and bacterial internalization.
abstract: Invasive bacterial pathogens often target cellular proteins involved in adhesion as a first event during infection. For example, Listeria monocytogenes uses the bacterial protein InlA to interact with E-cadherin, hijack the host adherens junction (AJ) machinery and invade non-phagocytic cells by a clathrin-dependent mechanism. Here, we investigate a potential role for clathrin in cell-cell adhesion. We observed that the initial steps of AJ formation trigger the phosphorylation of clathrin, and its transient localization at forming cell-cell contacts. Furthermore, we show that clathrin serves as a hub for the recruitment of proteins that are necessary for the actin rearrangements that accompany the maturation of AJs. Using an InlA/E-cadherin chimera, we show that adherent cells expressing the chimera form AJs with cells expressing E-cadherin. We demonstrate that non-adherent cells expressing the InlA chimera, as bacteria, can be internalized by E-cadherin-expressing adherent cells. Together these results reveal that a common clathrin-mediated machinery may regulate internalization and cell adhesion and that the relative mobility of one of the interacting partners plays an important role in the commitment to either one of these processes.
authors.affiliation: Institut Pasteur, Unité des Interactions Bactéries-Cellules, Paris, F-75015, France. matteo.bonazzi@cpbs.cnrs.fr
authors.forename: Matteo
authors.initials: M
authors.lastname: Bonazzi
authors.forename: Andreas
authors.initials: A
authors.lastname: Kühbacher
authors.forename: Alejandro
authors.initials: A
authors.lastname: Toledo-Arana
authors.forename: Adeline
authors.initials: A
authors.lastname: Mallet
authors.forename: Lavanya
authors.initials: L
authors.lastname: Vasudevan
authors.forename: Javier
authors.initials: J
authors.lastname: Pizarro-Cerdá
authors.forename: Frances M
authors.initials: FM
authors.lastname: Brodsky
authors.forename: Pascale
authors.initials: P
authors.lastname: Cossart
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism / Q000382:microbiology*; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion; D002966:Clathrin / Q000378:metabolism*; D004285:Dogs; D004705:Endocytosis; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D008089:Listeria monocytogenes / Q000472:pathogenicity; D061985:Madin Darby Canine Kidney Cells; D010766:Phosphorylation
chemical_list: D001426:Bacterial Proteins; D015820:Cadherins; D002966:Clathrin; C069761:internalin protein, Bacteria