title: Shigella effector IpaB-induced cholesterol relocation disrupts the Golgi complex and recycling network to inhibit host cell secretion.
abstract: Shigella infection causes destruction of the human colonic epithelial barrier. The Golgi network and recycling endosomes are essential for maintaining epithelial barrier function. Here we show that Shigella epithelial invasion induces fragmentation of the Golgi complex with consequent inhibition of both secretion and retrograde transport in the infected host cell. Shigella induces tubulation of the Rab11-positive compartment, thereby affecting cell surface receptor recycling. The molecular process underlying the observed damage to the Golgi complex and receptor recycling is a massive redistribution of plasma membrane cholesterol to the sites of Shigella entry. IpaB, a virulence factor of Shigella that is known to bind cholesterol, is necessary and sufficient to induce Golgi fragmentation and reorganization of the recycling compartment. Shigella infection-induced Golgi disorganization was also observed in vivo, suggesting that this mechanism affecting the sorting of cell surface molecules likely contributes to host epithelial barrier disruption associated with Shigella pathogenesis.
authors.affiliation: Institut Pasteur, Unité de Pathogénie Microbienne Moléculaire, 28 rue du Docteur Roux, 75724 Paris Cedex 15, France.
authors.forename: Joëlle
authors.initials: J
authors.lastname: Mounier
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Boncompain
authors.forename: Lidija
authors.initials: L
authors.lastname: Senerovic
authors.forename: Thibault
authors.initials: T
authors.lastname: Lagache
authors.forename: Fabrice
authors.initials: F
authors.lastname: Chrétien
authors.forename: Franck
authors.initials: F
authors.lastname: Perez
authors.forename: Michael
authors.initials: M
authors.lastname: Kolbe
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Olivo-Marin
authors.forename: Philippe J
authors.initials: PJ
authors.lastname: Sansonetti
authors.forename: Nathalie
authors.initials: N
authors.lastname: Sauvonnet
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism / Q000648:ultrastructure*; D006056:Golgi Apparatus / Q000378:metabolism / Q000648:ultrastructure*; D054884:Host-Pathogen Interactions; D006801:Humans; D008856:Microscopy, Fluorescence; D011506:Proteins / Q000378:metabolism*; D012760:Shigella / Q000472:pathogenicity*; D037521:Virulence Factors / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D011506:Proteins; D037521:Virulence Factors; C087447:ipaB protein, Shigella; D002784:Cholesterol