title: Induction of transient macroapertures in endothelial cells through RhoA inhibition by Staphylococcus aureus factors.
abstract: The GTPase RhoA is a major regulator of the assembly of actin stress fibers and the contractility of the actomyosin cytoskeleton. The epidermal cell differentiation inhibitor (EDIN) and EDIN-like ADP-ribosyltransferases of Staphylococcus aureus catalyze the inactivation of RhoA, producing actin cable disruption. We report that purified recombinant EDIN and EDIN-producing S. aureus provoke large transcellular tunnels in endothelial cells that we have named macroapertures (MAs). These structures open transiently, followed by the appearance of actin-containing membrane waves extending over the aperture. Disruption of actin cables, either directly or indirectly, through rhoA RNAi knockdown also triggers the formation of MAs. Intoxication of endothelial monolayers by EDIN produces a loss of barrier function and provides direct access of the endothelium basement membrane to S. aureus.
authors.affiliation: Toxines Bactériennes dans la Relation Hôte-Pathogènes, U627, Faculté de Médecine, Institut National de la Santé et de la Recherche Médicale, INSERM, 06107 Nice Cedex 2, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Boyer
authors.forename: Anne
authors.initials: A
authors.lastname: Doye
authors.forename: Monica
authors.initials: M
authors.lastname: Rolando
authors.forename: Gilles
authors.initials: G
authors.lastname: Flatau
authors.forename: Patrick
authors.initials: P
authors.lastname: Munro
authors.forename: Pierre
authors.initials: P
authors.lastname: Gounon
authors.forename: René
authors.initials: R
authors.lastname: Clément
authors.forename: Céline
authors.initials: C
authors.lastname: Pulcini
authors.forename: Michel R
authors.initials: MR
authors.lastname: Popoff
authors.forename: Amel
authors.initials: A
authors.lastname: Mettouchi
authors.forename: Luce
authors.initials: L
authors.lastname: Landraud
authors.forename: Olivier
authors.initials: O
authors.lastname: Dussurget
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Lemichez
mesh_terms: D036002:ADP Ribose Transferases / Q000302:isolation & purification / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000302:isolation & purification / Q000494:pharmacology*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure*; D006801:Humans; D008969:Molecular Sequence Data; D034622:RNA Interference / Q000502:physiology; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000737:chemistry / Q000201:enzymology; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D011994:Recombinant Proteins; C067120:epidermal cell differentiation inhibitor, Staphylococcus aureus; D036002:ADP Ribose Transferases; D020742:rhoA GTP-Binding Protein