Jeng Robert L, Goley Erin D, D'Alessio Joseph A, Chaga Oleg Y, Svitkina Tatyana M, Borisy Gary G, Heinzen Robert A, Welch Matthew D
Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA.
Cell Microbiol. 2004 Aug;6(8):761-9. doi: 10.1111/j.1462-5822.2004.00402.x.
Spotted fever group Rickettsia are obligate intracellular pathogens that exploit the host cell actin cytoskeleton to promote motility and cell-to-cell spread. Although other pathogens such as Listeria monocytogenes use an Arp2/3 complex-dependent nucleation mechanism to generate comet tails consisting of Y-branched filament arrays, Rickettsia polymerize tails consisting of unbranched filaments by a previously unknown mechanism. We identified genes in several Rickettsia species encoding proteins (termed RickA) with similarity to the WASP family of Arp2/3-complex activators. Rickettsia rickettsii RickA activated both the nucleation and Y-branching activities of the Arp2/3 complex like other WASP-family proteins, and was sufficient to direct the motility of microscopic beads in cell extracts. Actin tails generated by RickA-coated beads consisted of Y-branched filament networks. These data suggest that Rickettsia use an Arp2/3 complex-dependent actin-nucleation mechanism similar to that of other pathogens. We propose that additional Rickettsia or host factors reorganize the Y-branched networks into parallel arrays in a manner similar to a recently proposed model of filopodia formation.
斑点热群立克次氏体是专性细胞内病原体，它们利用宿主细胞的肌动蛋白细胞骨架来促进运动性和细胞间传播。尽管其他病原体，如单核细胞增生李斯特菌，利用一种依赖Arp2/3复合物的成核机制来产生由Y形分支丝状阵列组成的彗星尾，但立克次氏体通过一种此前未知的机制聚合由无分支细丝组成的尾。我们在几种立克次氏体物种中鉴定出了编码与Arp2/3复合物激活剂的WASP家族相似的蛋白质（称为RickA）的基因。立氏立克次氏体的RickA像其他WASP家族蛋白质一样激活了Arp2/3复合物的成核和Y形分支活性，并且足以指导细胞提取物中微小珠子的运动。由包被RickA的珠子产生的肌动蛋白尾由Y形分支丝状网络组成。这些数据表明立克次氏体使用一种与其他病原体类似的依赖Arp2/3复合物的肌动蛋白成核机制。我们提出，其他立克次氏体或宿主因子以类似于最近提出的丝状伪足形成模型的方式将Y形分支网络重新组织成平行阵列。
