title: ATP-mediated Erk1/2 activation stimulates bacterial capture by filopodia, which precedes Shigella invasion of epithelial cells.
abstract: Shigella, the causative agent of bacillary dysentery in humans, invades epithelial cells, using a type III secretory system (T3SS) to inject bacterial effectors into host cells and remodel the actin cytoskeleton. ATP released through connexin hemichanels on the epithelial membrane stimulates Shigella invasion and dissemination in epithelial cells. Here, we show that prior to contact with the cell body, Shigella is captured by nanometer-thin micropodial extensions (NMEs) at a distance from the cell surface, in a process involving the T3SS tip complex proteins and stimulated by ATP- and connexin-mediated signaling. Upon bacterial contact, NMEs retract, bringing bacteria in contact with the cell body, where invasion occurs. ATP stimulates Erk1/2 activation, which controls actin retrograde flow in NMEs and their retraction. These findings reveal previously unappreciated facets of interaction of an invasive bacterium with host cells and a prominent role for Erk1/2 in the control of filopodial dynamics.
authors.affiliation: Equipe Communication Intercellulaire et Infections Microbiennes, Centre de Recherche Interdisciplinaire en Biologie, Collège de France, 75005 Paris, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Romero
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Grompone
authors.forename: Nathalie
authors.initials: N
authors.lastname: Carayol
authors.forename: Joëlle
authors.initials: J
authors.lastname: Mounier
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Guadagnini
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Prevost
authors.forename: Philippe J
authors.initials: PJ
authors.lastname: Sansonetti
authors.forename: Guy Tran
authors.initials: GT
authors.lastname: Van Nhieu
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D004405:Dysentery, Bacillary / Q000201:enzymology* / Q000378:metabolism / Q000382:microbiology* / Q000503:physiopathology; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000201:enzymology / Q000378:metabolism / Q000382:microbiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism*; D011554:Pseudopodia / Q000201:enzymology / Q000378:metabolism / Q000382:microbiology*; D012760:Shigella / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D001426:Bacterial Proteins; D000255:Adenosine Triphosphate; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3