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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ADP Ribose Transferases / isolation & purification
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ADP Ribose Transferases / pharmacology*
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Bacterial Proteins / isolation & purification
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Bacterial Proteins / pharmacology*
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Cells, Cultured
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Endothelial Cells / drug effects
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Endothelial Cells / metabolism*
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Endothelial Cells / ultrastructure*
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Humans
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Molecular Sequence Data
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RNA Interference / physiology
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Recombinant Proteins / isolation & purification
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Recombinant Proteins / pharmacology
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Staphylococcus aureus / chemistry
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Staphylococcus aureus / enzymology
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rhoA GTP-Binding Protein / antagonists & inhibitors*
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rhoA GTP-Binding Protein / genetics
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rhoA GTP-Binding Protein / metabolism
Substances
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Bacterial Proteins
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Recombinant Proteins
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epidermal cell differentiation inhibitor, Staphylococcus aureus
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ADP Ribose Transferases
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rhoA GTP-Binding Protein
Associated data
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GENBANK/AJ277173
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RefSeq/NC_003265