Gouin Edith, Egile Coumaran, Dehoux Pierre, Villiers Véronique, Adams Josephine, Gertler Frank, Li Rong, Cossart Pascale
Unité des Interactions Bactéries-Cellules, Institut Pasteur, 28 Rue du Docteur Roux, Paris 75015, France.
Nature. 2004 Jan 29;427(6973):457-61. doi: 10.1038/nature02318.
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. 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. 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.
肌动蛋白聚合是细胞运动的主要驱动力，细菌李斯特菌、志贺氏菌以及痘苗病毒在细胞内和细胞间运动时也会利用这一机制。开创性研究表明，Arp2/3复合物在肌动蛋白成核以及在膜延伸和病原体运动过程中生成肌动蛋白丝分支阵列方面具有关键作用。Arp2/3需要诸如WASP家族蛋白或李斯特菌的ActA等蛋白质激活。我们之前报道过，另一种细胞内细菌康氏立克次体的肌动蛋白尾与李斯特菌、志贺氏菌或痘苗病毒的不同，它由明显不含Arp2/3的长直肌动蛋白丝组成（参考文献4）。在此我们鉴定出一种康氏立克次体表面蛋白RickA，它在体外能激活Arp2/3，不过效率比ActA低。在受感染细胞中，Arp2/3在立克次体表面可检测到，但在肌动蛋白尾中未检测到。当在哺乳动物细胞中表达并靶向至细胞膜时，RickA会诱导丝状伪足形成。因此，RickA诱导的肌动蛋白聚合通过生成类似于丝状伪足中存在的长肌动蛋白丝，有潜力成为研究丝状伪足形成的工具。
