INSERM, U, Université de Nice-Sophia-Antipolis, Centre Méditerranéen de Médecine Moléculaire, Nice, France.
Cell Host Microbe. 2011 Nov 17;10(5):464-74. doi: 10.1016/j.chom.2011.09.014.
RhoA-inhibitory bacterial toxins, such as Staphylococcus aureus EDIN toxin, induce large transendothelial cell macroaperture (TEM) tunnels that rupture the host endothelium barrier and promote bacterial dissemination. Host cells repair these tunnels by extending actin-rich membrane waves from the TEM edges. We reveal that cyclic-AMP signaling produced by Bacillus anthracis edema toxin (ET) also induces TEM formation, which correlates with increased vascular permeability. We show that ET-induced TEM formation resembles liquid dewetting, a physical process of nucleation and growth of holes within a thin liquid film. We also identify the cellular mechanisms of tunnel closure and reveal that the I-BAR domain protein Missing in Metastasis (MIM) senses de novo membrane curvature generated by the TEM, accumulates at the TEM edge, and triggers Arp2/3-dependent actin polymerization, which induces actin-rich membrane waves that close the TEM. Thus, the balance between ET-induced TEM formation and resealing likely determines the integrity of the host endothelium barrier.
RhoA 抑制性细菌毒素，如金黄色葡萄球菌 EDIN 毒素，诱导大的跨内皮细胞大孔（TEM）隧道，破坏宿主内皮屏障并促进细菌传播。宿主细胞通过从 TEM 边缘延伸富含肌动蛋白的膜波来修复这些隧道。我们揭示炭疽杆菌水肿毒素（ET）产生的环 AMP 信号也诱导 TEM 的形成，这与血管通透性的增加相关。我们表明，ET 诱导的 TEM 形成类似于液体去湿，这是一个在薄液膜内形成孔的成核和生长的物理过程。我们还确定了隧道闭合的细胞机制，并揭示了转移性缺失（MIM）蛋白识别由 TEM 产生的新的膜曲率，在 TEM 边缘积累，并触发 Arp2/3 依赖性肌动蛋白聚合，这诱导富含肌动蛋白的膜波闭合 TEM。因此，ET 诱导的 TEM 形成和再封闭之间的平衡可能决定了宿主内皮屏障的完整性。
