title: Apical invasion of intestinal epithelial cells by Salmonella typhimurium requires villin to remodel the brush border actin cytoskeleton.
abstract: Salmonella invasion of intestinal epithelial cells requires extensive, though transient, actin modifications at the site of bacterial entry. The actin-modifying protein villin is present in the brush border where it participates in the constitution of microvilli and in epithelial restitution after damage through its actin-severing activity. We investigated a possible role for villin in Salmonella invasion. The absence of villin, which is normally located at the bacterial entry site, leads to a decrease in Salmonella invasion. Villin is necessary for early membrane-associated processes and for optimal ruffle assembly by balancing the steady-state level of actin. The severing activity of villin is important for Salmonella invasion in vivo. The bacterial phosphatase SptP tightly regulates villin phosphorylation, while the actin-binding effector SipA protects F-actin and counterbalances villin-severing activity. Thus, villin plays an important role in establishing the balance between actin polymerization and actin severing to facilitate the initial steps of Salmonella entry.
authors.affiliation: Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, 25 rue du Docteur Roux, 75015 Paris, France; INSERM U786, Institut Pasteur, 25 rue du Docteur Roux, 75015 Paris, France.
authors.forename: Nouara
authors.initials: N
authors.lastname: Lhocine
authors.affiliation: Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, 25 rue du Docteur Roux, 75015 Paris, France; INSERM U786, Institut Pasteur, 25 rue du Docteur Roux, 75015 Paris, France.
authors.forename: Ellen T
authors.initials: ET
authors.lastname: Arena
authors.affiliation: Plateforme de Microscopie Ultrastructurale, Institut Pasteur, 25 rue du Docteur Roux, 75015 Paris, France.
authors.forename: Perrine
authors.initials: P
authors.lastname: Bomme
authors.affiliation: Unité Mixte de Recherche 144, Institut Curie, 75248 Paris Cedex 05, France; Centro de Estudos de Doenças Crónicas (CEDOC), Faculdade de Ciencias Médicas, Universidade Nova de Lisboa, 1169-056, Portugal.
authors.forename: Florent
authors.initials: F
authors.lastname: Ubelmann
authors.affiliation: Plateforme de Microscopie Ultrastructurale, Institut Pasteur, 25 rue du Docteur Roux, 75015 Paris, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Prévost
authors.affiliation: Unité Mixte de Recherche 144, Institut Curie, 75248 Paris Cedex 05, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Robine
authors.affiliation: Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, 25 rue du Docteur Roux, 75015 Paris, France; INSERM U786, Institut Pasteur, 25 rue du Docteur Roux, 75015 Paris, France; Collège de France, 11 Place Marcelin Berthelot, 75005 Paris, France. Electronic address: philippe.sansonetti@pasteur.fr.
authors.forename: Philippe J
authors.initials: PJ
authors.lastname: Sansonetti
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism; D002460:Cell Line; D004705:Endocytosis; D004847:Epithelial Cells / Q000382:microbiology / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D007413:Intestinal Mucosa / Q000382:microbiology / Q000502:physiology; D008840:Microfilament Proteins / Q000378:metabolism*; D008871:Microvilli / Q000382:microbiology / Q000502:physiology*; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D012486:Salmonella typhimurium / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; D008840:Microfilament Proteins; C118287:SipA protein, Salmonella; C026615:villin; D017027:Protein Tyrosine Phosphatases; C439890:sptP protein, Salmonella typhimurium