Induction of transient macroapertures in endothelial cells through RhoA inhibition by Staphylococcus aureus factors - RNAi

Induction of transient macroapertures in endothelial cells through RhoA inhibition by Staphylococcus aureus factors
June 5, 2006
Laurent Boyer, Anne Doye, Monica Rolando, Gilles Flatau, Patrick Munro, Pierre Gounon, Ren? Cl?ment, C?line Pulcini, Michel R. Popoff, Amel Mettouchi, Luce Landraud, Olivier Dussurget, and Emmanuel Lemichez
Journal of Cell Biology
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.
L. Boyer and A. Doye contributed equally to this paper
Abbreviations used in this paper: EDIN, epidermal cell differentiation inhibitor; HMVEC, human microvascular endothelial cell; HUVEC, human umbilical vein endothelial cell; MA, macroaperture; RhoGDI, Rho guanine nucleotide dissociation inhibitor; ROCK, Rho kinase; SFM, serum-free medium; VVO, vesiculo-vacuolar organelle; WGA, wheat germ agglutinin.
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