Rickettsia Sca2 is a bacterial formin-like mediator of actin-based motility.

Rickettsia Sca2 is a bacterial formin-like mediator of actin-based motility.
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DOI:
10.1038/ncb2109
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发表时间:
2010-11
影响因子:
21.3
通讯作者:
Welch MD
Welch MD
中科院分区:
生物学1区
文献类型:
--
作者:
Haglund CM;Choe JE;Skau CT;Kovar DR;Welch MD

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不同的细胞内病原体颠覆宿主肌动蛋白聚合机制,在感染期间驱动细胞内和细胞间的移动。斑点热组(SFG)中的立克次体是革兰氏阴性的专性细胞内细菌病原体,它们经历基于肌动蛋白的运动,并组装由长长的、无分支的肌动蛋白细丝组成的独特的“彗星尾巴”。尽管有这种不同的组织结构,但有人认为,立克次体彗星尾巴中的肌动蛋白是由宿主Arp2/3复合体和细菌蛋白RickA组成的,它们组装了分支肌动蛋白网络。然而,第二个细菌基因sca2最近与立克次杆菌肌动蛋白尾巴的形成有关。在这里,我们证明了sca2是一种细菌肌动蛋白组装因子,它在功能上模仿真核细胞的Forin蛋白。SCA2使未分支的肌动蛋白细丝成核,与生长的带刺末端连续结合,需要Profilin才能有效地延长,并抑制覆盖蛋白的活性,所有这些特性都与Forins相同。ScA2定位于立克次体表面,足以促进肌动蛋白细丝在细胞质提取液中的组装。这些结果表明,sca2模拟福尔马林来确定尾部立克次体中肌动蛋白细丝的独特组织,并驱动细菌的运动,而不依赖于宿主核因子。
Diverse intracellular pathogens subvert the host actin polymerization machinery to drive movement within and between cells during infection. Rickettsia in the spotted fever group (SFG) are Gram-negative, obligate intracellular bacterial pathogens that undergo actin-based motility and assemble distinctive ‘comet tails’ that consist of long, unbranched actin filaments. Despite this distinct organization, it was proposed that actin in Rickettsia comet tails is nucleated by the host Arp2/3 complex and the bacterial protein RickA, which assemble branched actin networks. However, a second bacterial gene, sca2, was recently implicated in actin tail formation by R. rickettsii. Here, we demonstrate that Sca2 is a bacterial actin-assembly factor that functionally mimics eukaryotic formin proteins. Sca2 nucleates unbranched actin filaments, processively associates with growing barbed ends, requires profilin for efficient elongation, and inhibits the activity of capping protein, all properties shared with formins. Sca2 localizes to the Rickettsia surface and is sufficient to promote the assembly of actin filaments in cytoplasmic extract. These results suggest that Sca2 mimics formins to determine the unique organization of actin filaments in Rickettsia tails and drive bacterial motility, independently of host nucleators.
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