Department of Microbial Pathogenesis, Boyer Center for Molecular Medicine, Yale School of Medicine, New Haven, CT 06536, USA.
J Cell Sci. 2014 Jan 1;127(Pt 1):240-9. doi: 10.1242/jcs.140038. Epub 2013 Oct 23.
Several bacterial pathogens hijack the actin assembly machinery and display intracellular motility in the cytosol of infected cells. At the cell cortex, intracellular motility leads to bacterial dissemination through formation of plasma membrane protrusions that resolve into vacuoles in adjacent cells. Here, we uncover a crucial role for actin network disassembly in dissemination of Listeria monocytogenes. We found that defects in the disassembly machinery decreased the rate of actin tail turnover but did not affect the velocity of the bacteria in the cytosol. By contrast, defects in the disassembly machinery had a dramatic impact on bacterial dissemination. Our results suggest a model of L. monocytogenes dissemination in which the disassembly machinery, through local recycling of the actin network in protrusions, fuels continuous actin assembly at the bacterial pole and concurrently exhausts cytoskeleton components from the network distal to the bacterium, which enables membrane apposition and resolution of protrusions into vacuoles.
几种细菌病原体劫持肌动蛋白组装机制,并在感染细胞的细胞质中表现出细胞内运动性。在细胞膜皮质,细胞内运动导致细菌通过形成质膜突起而传播,这些突起在相邻细胞中分解成空泡。在这里,我们揭示了肌动蛋白网络解体在李斯特菌传播中的关键作用。我们发现,解体机制的缺陷降低了肌动蛋白尾部的周转率,但不影响细胞质中细菌的速度。相比之下,解体机制的缺陷对细菌的传播有巨大的影响。我们的结果表明,李斯特菌传播的模型是通过突起中肌动蛋白网络的局部回收,解体机制为细菌极的持续肌动蛋白组装提供动力,同时耗尽远离细菌的网络中的细胞骨架成分,从而使膜贴合,并将突起分解为空泡。