Welch M D, Iwamatsu A, Mitchison T J
Department of Cellular and Molecular Pharmacology, University of California at San Francisco, 94143, USA.
Nature. 1997 Jan 16;385(6613):265-9. doi: 10.1038/385265a0.
The pathogenic bacterium Listeria monocytogenes is capable of directed movement within the cytoplasm of infected host cells. Propulsion is thought to be driven by actin polymerization at the bacterial cell surface, and moving bacteria leave in their wake a tail of actin filaments. Determining the mechanism by which L. monocytogenes polymerizes actin may aid the understanding of how actin polymerization is controlled in the cell. Actin assembly by L. monocytogenes requires the bacterial surface protein ActA and protein components present in host cell cytoplasm. We have purified an eight-polypeptide complex that possesses the properties of the host-cell actin polymerization factor. The pure complex is sufficient to initiate ActA-dependent actin polymerization at the surface of L. monocytogenes, and is required to mediate actin tail formation and motility. Two subunits of this protein complex are actin-related proteins (ARPs) belonging to the Arp2 and Arp3 subfamilies. The Arp3 subunit localizes to the surface of stationary bacteria and the tails of motile bacteria in tissue culture cells infected with L. monocytogenes; this is consistent with a role for the complex in promoting actin assembly in vivo. The activity and subunit composition of the Arp2/3 complex suggests that it forms a template that nucleates actin polymerization.
致病性细菌单核细胞增生李斯特菌能够在被感染宿主细胞的细胞质内进行定向移动。据认为,其推进力是由细菌细胞表面的肌动蛋白聚合作用驱动的,移动的细菌身后会留下一条肌动蛋白丝尾。确定单核细胞增生李斯特菌聚合肌动蛋白的机制,可能有助于理解细胞中肌动蛋白聚合作用是如何被控制的。单核细胞增生李斯特菌的肌动蛋白组装需要细菌表面蛋白ActA和宿主细胞质中存在的蛋白质成分。我们纯化了一种具有宿主细胞肌动蛋白聚合因子特性的八多肽复合物。这种纯复合物足以在单核细胞增生李斯特菌表面引发依赖ActA的肌动蛋白聚合作用,并且是介导肌动蛋白尾形成和运动所必需的。该蛋白质复合物的两个亚基是属于Arp2和Arp3亚家族的肌动蛋白相关蛋白(ARP)。在感染了单核细胞增生李斯特菌的组织培养细胞中,Arp3亚基定位于静止细菌的表面和运动细菌的尾部;这与该复合物在体内促进肌动蛋白组装的作用一致。Arp2/3复合物的活性和亚基组成表明它形成了一个使肌动蛋白聚合作用成核的模板。