Contractile actin cables induced by Bacillus anthracis lethal toxin depend on the histone acetylation machinery. Issue 10 (4th November 2015)

• Record Type: Journal Article
• Authors: Rolando, Monica; Stefani, Caroline; Doye, Anne; Acosta, Maria I.; Visvikis, Orane; Yevick, Hannah G.; Buchrieser, Carmen; Mettouchi, Amel; Bassereau, Patricia; Lemichez, Emmanuel
• Is Part Of: Cytoskeleton. Volume 72:Issue 10(2015:Oct.)
• Page Start: 542
• Page End: 556
• Publication Date: 2015-11-04
• Subjects: Bacillus anthracis toxin -- HAT -- HDAC -- gene expression -- actin cytoskeleton -- vascular permeability; Cytoskeleton -- Periodicals; 571.65405
• DOI: 10.1002/cm.21256
• Languages: English
• ISSNs: 1949-3584

Abstract

Abstract : It remains a challenge to decode the molecular basis of the long‐term actin cytoskeleton rearrangements that are governed by the reprogramming of gene expression. Bacillus anthracis lethal toxin (LT) inhibits mitogen‐activated protein kinase (MAPK) signaling, thereby modulating gene expression, with major consequences for actin cytoskeleton organization and the loss of endothelial barrier function. Using a laser ablation approach, we characterized the contractile and tensile mechanical properties of LT‐induced stress fibers. These actin cables resist pulling forces that are transmitted at cell–matrix interfaces and at cell–cell discontinuous adherens junctions. We report that treating the cells with trichostatin A (TSA), a broad range inhibitor of histone deacetylases (HDACs), or with MS‐275, which targets HDAC1, 2 and 3, induces stress fibers. LT decreased the cellular levels of HDAC1, 2 and 3 and reduced the global HDAC activity in the nucleus. Both the LT and TSA treatments induced Rnd3 expression, which is required for the LT‐mediated induction of actin stress fibers. Furthermore, we reveal that treating the LT‐intoxicated cells with garcinol, an inhibitor of histone acetyl‐transferases (HATs), disrupts the stress fibers and limits the monolayer barrier dysfunctions. These data demonstrate the importance of modulating the flux of protein acetylation in order to control actin cytoskeleton organization and the endothelial cell monolayer barrier. © 2015 Wiley Periodicals, Inc.