Bugalhão Joana N, Mota Luís Jaime, Franco Irina S
UCIBIO-REQUIMTE, Departamento de Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal.
UCIBIO-REQUIMTE, Departamento de Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, 2780-157 Oeiras, Portugal
Pathog Dis. 2015 Dec;73(9):ftv078. doi: 10.1093/femspd/ftv078. Epub 2015 Sep 27.
The actin cytoskeleton is a key target of numerous microbial pathogens, including protozoa, fungi, bacteria and viruses. In particular, bacterial pathogens produce and deliver virulence effector proteins that hijack actin dynamics to enable bacterial invasion of host cells, allow movement within the host cytosol, facilitate intercellular spread or block phagocytosis. Many of these effector proteins directly or indirectly target the major eukaryotic actin nucleator, the Arp2/3 complex, by either mimicking nucleation promoting factors or activating upstream small GTPases. In contrast, this review is focused on a recently identified class of effector proteins from Gram-negative bacteria that function as direct actin nucleators. These effector proteins mimic functional activities of formins, WH2-nucleators and Ena/VASP assembly promoting factors demonstrating that bacteria have coopted the complete set of eukaryotic actin assembly pathways. Structural and functional analyses of these nucleators have revealed several motifs and/or mechanistic activities that are shared with eukaryotic actin nucleators. However, functional effects of these proteins during infection extend beyond plain actin polymerization leading to interference with other host cell functions such as vesicle trafficking, cell cycle progression and cell death. Therefore, their use as model systems could not only help in the understanding of the mechanistic details of actin polymerization but also provide novel insights into the connection between actin dynamics and other cellular pathways.
肌动蛋白细胞骨架是众多微生物病原体的关键靶点，这些病原体包括原生动物、真菌、细菌和病毒。特别是，细菌病原体产生并递送毒力效应蛋白，这些蛋白劫持肌动蛋白动力学，以使细菌能够侵入宿主细胞、在宿主细胞质内移动、促进细胞间传播或阻止吞噬作用。许多这些效应蛋白通过模拟成核促进因子或激活上游小GTP酶，直接或间接靶向主要的真核肌动蛋白成核剂Arp2/3复合体。相比之下，本综述聚焦于最近从革兰氏阴性菌中鉴定出的一类效应蛋白，它们作为直接的肌动蛋白成核剂发挥作用。这些效应蛋白模拟了formin、WH2成核剂和Ena/VASP组装促进因子的功能活性，表明细菌已经采用了全套真核肌动蛋白组装途径。对这些成核剂的结构和功能分析揭示了一些与真核肌动蛋白成核剂共有的基序和/或机制活性。然而，这些蛋白在感染过程中的功能作用不仅限于简单的肌动蛋白聚合，还会干扰其他宿主细胞功能，如囊泡运输、细胞周期进程和细胞死亡。因此，将它们用作模型系统不仅有助于理解肌动蛋白聚合的机制细节，还能为肌动蛋白动力学与其他细胞途径之间的联系提供新的见解。
