Membrane-dependent actin polymerization mediated by the Legionella pneumophila effector protein MavH.
Membrane-dependent actin polymerization mediated by the Legionella pneumophila effector protein MavH.
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DOI：
10.1371/journal.ppat.1011512
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发表时间：
2023-07
期刊：
影响因子：
6.7
通讯作者：
Mao, Yuxin
中科院分区：
文献类型：
--
作者：
Zhang, Qing;Wan, Min;Kudryashova, Elena;Kudryashov, Dmitri;Mao, Yuxin
嗜肺军团菌在真核细胞中的特殊生态位（含军团菌的液泡（LCV））中繁殖。感染过程由通过 IV 型分泌系统传递的 330 多种效应蛋白控制。在本研究中，我们报告军团菌 MavH 效应子定位于内体，并在异位表达时以磷脂酰肌醇 3-磷酸 (PI(3)P) 依赖性方式重塑宿主肌动蛋白细胞骨架。我们发现，MavH 分别通过其 CP 相互作用 (CPI) 基序和 WH2 样肌动蛋白结合域将宿主肌动蛋白帽蛋白 (CP) 和肌动蛋白招募到内体。体外测定表明，MavH 刺激肌动蛋白在含 PI(3)P 的脂质体上组装，从而导致其形成管状结构。此外，MavH 招募 CP 会负向调节膜上的 F-肌动蛋白密度。我们进一步表明，在嗜肺军团菌感染的细胞中，MavH 在感染的早期阶段就出现在 LCV 周围，并促进细菌进入宿主。总之，我们的结果揭示了由 MavH 催化的膜依赖性肌动蛋白聚合诱导的膜管化的新机制，通过调节宿主肌动蛋白动力学，有助于嗜肺军团菌感染的早期阶段。嗜肺军团菌是 1976 年发现的一种细菌，可引起严重的肺部感染，称为军团病。吸入受污染的气溶胶后，嗜肺军团菌会释放超过 330 种细菌蛋白，以促进其细胞内存活和增殖。这些分泌的细菌蛋白靶向多种宿主细胞途径，包括肌动蛋白细胞骨架。在这项研究中，我们重点研究了一种嗜肺军团菌分泌蛋白，称为 MavH。我们发现MavH在体外和体内促进肌动蛋白在膜表面的组装，并且MavH引发的肌动蛋白聚合进一步驱动膜的变形和管状化。此外，我们发现MavH通过调节宿主肌动蛋白动力学来促进细菌进入宿主细胞。总之，我们确定 MavH 是一种新型肌动蛋白调节剂，可诱导肌动蛋白聚合依赖性膜管状结构并增强嗜肺军团菌感染宿主的能力。
L. pneumophila propagates in eukaryotic cells within a specialized niche, the Legionella-containing vacuole (LCV). The infection process is controlled by over 330 effector proteins delivered through the type IV secretion system. In this study, we report that the Legionella MavH effector localizes to endosomes and remodels host actin cytoskeleton in a phosphatidylinositol 3-phosphate (PI(3)P) dependent manner when ectopically expressed. We show that MavH recruits host actin capping protein (CP) and actin to the endosome via its CP-interacting (CPI) motif and WH2-like actin-binding domain, respectively. In vitro assays revealed that MavH stimulates actin assembly on PI(3)P-containing liposomes causing their tubulation. In addition, the recruitment of CP by MavH negatively regulates F-actin density at the membrane. We further show that, in L. pneumophila-infected cells, MavH appears around the LCV at the very early stage of infection and facilitates bacterium entry into the host. Together, our results reveal a novel mechanism of membrane tubulation induced by membrane-dependent actin polymerization catalyzed by MavH that contributes to the early stage of L. pneumophila infection by regulating host actin dynamics. Legionella pneumophila, a bacterium discovered in 1976, can cause a severe lung infection known as Legionnaires’ disease. Upon inhalation of contaminated aerosol, L. pneumophila releases over 330 bacterial proteins to facilitate its intracellular survival and proliferation. These secreted bacterial proteins target a variety of host cellular pathways, including the actin cytoskeleton. In this study, we focused on one of such secreted L. pneumophila proteins, called MavH. We found that MavH promotes actin assembly both in vitro and in vivo on the membrane surface and actin polymerization triggered by MavH further drives the deformation and tubulation of the membrane. Moreover, we found that MavH promotes the entry of the bacterium into host cells by regulating host actin dynamics. In summary, we identified MavH as a novel actin regulator that induces actin polymerization-dependent membrane tubulation and enhances the ability of L. pneumophila to infect its host.
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DOI：
10.1126/science.1227026
发表时间：
2012-11-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Choy A;Dancourt J;Mugo B;O'Connor TJ;Isberg RR;Melia TJ;Roy CR
通讯作者：
Roy CR
影响因子：
3.4
作者：
Aitken, Colin Echeverria;Marshall, R. Andrew;Puglisi, Joseph D.
通讯作者：
Puglisi, Joseph D.
影响因子：
64.5
作者：
Ahuja, Rashmi;Pinyol, Roser;Qualmann, Britta
通讯作者：
Qualmann, Britta
影响因子：
5.6
作者：
通讯作者：
--
影响因子：
3.6
作者：
Duménil, G;Isberg, RR
通讯作者：
Isberg, RR