The RickA protein of Rickettsia conorii activates the Arp2/3 complex

The RickA protein of Rickettsia conorii activates the Arp2/3 complex
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DOI:
10.1038/nature02318
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发表时间:
2004-01-29
期刊:
影响因子:
64.8
通讯作者:
Cossart, P
Cossart, P
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Gouin, E;Egile, C;Cossart, P

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肌动蛋白聚合是细胞运动的主要驱动力,也被李斯特菌、志贺氏菌和牛痘病毒用于细胞内和细胞间运动(1,2)。精液研究表明,Arp 2/3复合物在细胞膜延伸和病原体运动过程中使肌动蛋白成核并产生肌动蛋白丝的分支阵列中具有关键功能(3)。Arp 2/3需要被WASP家族蛋白或李斯特菌ActA等蛋白质激活。我们以前报道过,与李斯特菌、志贺氏菌或牛痘菌不同,另一种细胞内细菌康氏立克次氏体的肌动蛋白尾部是由明显缺乏Arp 2/3的长而不分支的肌动蛋白丝组成的(参考文献4)。在这里,我们确定了一个R。Conorii表面蛋白RickA在体外激活Arp 2/3,尽管不如ActA有效。在感染的细胞中,Arp 2/3在立克次体表面检测到,但不在肌动蛋白尾中。当在哺乳动物细胞中表达并靶向细胞膜时,RickA诱导丝状伪足。因此,RickA诱导的肌动蛋白聚合,通过产生长的肌动蛋白丝,让人想起那些存在于丝状伪足,有可能作为一种工具,研究丝状伪足的形成。
Actin polymerization, the main driving force for cell locomotion, is also used by the bacteria Listeria and Shigella and vaccinia virus for intracellular and intercellular movements(1,2). Seminal studies have shown the key function of the Arp2/3 complex in nucleating actin and generating a branched array of actin filaments during membrane extension and pathogen movement(3). Arp2/3 requires activation by proteins such as the WASP-family proteins or ActA of Listeria. We previously reported that actin tails of Rickettsia conorii, another intracellular bacterium, unlike those of Listeria, Shigella or vaccinia, are made of long unbranched actin filaments apparently devoid of Arp2/3 (ref. 4). Here we identify a R. conorii surface protein, RickA, that activates Arp2/3 in vitro, although less efficiently than ActA. In infected cells, Arp2/3 is detected on the rickettsial surface but not in actin tails. When expressed in mammalian cells and targeted to the membrane, RickA induces filopodia. Thus RickA-induced actin polymerization, by generating long actin filaments reminiscent of those present in filopodia, has potential as a tool for studying filopodia formation.