Chong Ryan, Swiss Rachel, Briones Gabriel, Stone Kathryn L, Gulcicek Erol E, Agaisse Hervé
Section of Microbial Pathogenesis, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, CT, USA.
Cell Host Microbe. 2009 Sep 17;6(3):268-78. doi: 10.1016/j.chom.2009.08.006.
The actin-based motility of the intracellular pathogen Listeria monocytogenes relies on ActA, a bacterial factor with a structural domain allowing it to mimic the actin nucleation-promoting activity of host cell proteins of the WASP/WAVE family. Here, we used an RNAi-based genetic approach in combination with computer-assisted image analysis to investigate the role of host factors in L. monocytogenes cell-to-cell spread. We showed that the host cell serine/threonine kinase CK2 is required for efficient actin tail formation by L. monocytogenes. Furthermore, CK2-mediated phosphorylation of ActA regulated its affinity for the actin-nucleating ARP2/3 complex, as is the case for CK2-mediated phosphorylation of WASP and WAVE. Thus, ActA not only displays structural mimicry of WASP/WAVE family members, but also regulatory mimicry, having precisely co-opted the host machinery regulating these proteins. Comparisons based on ActA amino acid sequence suggest that unrelated pathogens that display actin-based motility may have evolved a similar strategy of regulatory mimicry.
细胞内病原体单核细胞增生李斯特菌基于肌动蛋白的运动性依赖于ActA，ActA是一种细菌因子，其结构域使其能够模拟WASP/WAVE家族宿主细胞蛋白的肌动蛋白成核促进活性。在此，我们使用基于RNA干扰的遗传方法并结合计算机辅助图像分析，来研究宿主因子在单核细胞增生李斯特菌细胞间传播中的作用。我们发现，宿主细胞丝氨酸/苏氨酸激酶CK2是单核细胞增生李斯特菌有效形成肌动蛋白尾所必需的。此外，CK2介导的ActA磷酸化调节了其对肌动蛋白成核ARP2/3复合物的亲和力，WASP和WAVE的CK2介导的磷酸化情况也是如此。因此，ActA不仅在结构上模拟了WASP/WAVE家族成员，而且在调节上也进行了模拟，精确地采用了调节这些蛋白的宿主机制。基于ActA氨基酸序列的比较表明，表现出基于肌动蛋白运动性的无关病原体可能已经进化出类似的调节模拟策略。
