Rickettsia parkeri invasion of diverse host cells involves an Arp2/3 complex, WAVE complex and Rho-family GTPase-dependent pathway.
Rickettsia parkeri invasion of diverse host cells involves an Arp2/3 complex, WAVE complex and Rho-family GTPase-dependent pathway.
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DOI：
10.1111/j.1462-5822.2011.01739.x
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发表时间：
2012-04
影响因子：
3.4
通讯作者：
Welch MD
中科院分区：
文献类型：
--
作者：
Reed SC;Serio AW;Welch MD
立克次体是专性细胞内病原体，通过节肢动物传播给人类，并引起斑点热和斑疹伤寒等疾病。虽然立克次体需要宿主细胞肌动蛋白细胞骨架的入侵，介导这一过程的细胞骨架蛋白尚未完全描述。为了鉴定斑点热组（SFG）成员之一的帕克氏立克次体（Rickettsia parkeri）在细胞入侵过程中的重要宿主因子，我们在果蝇S2 R+细胞中进行了靶向105个蛋白质的RNAi筛选。筛选鉴定了21种对入侵重要的核心蛋白，包括GTP酶Rac 1和Rac 2、WAVE成核促进因子复合物和Arp 2/3复合物。在包括内皮细胞在内的哺乳动物细胞中，R. parkeri，Arp 2/3复合物也是入侵的关键，而WAVE 2以及Rho GTP酶的需求取决于特定的细胞类型。我们建议R. parkeri通过导致肌动蛋白成核的主要途径侵入S2 R+节肢动物细胞，而哺乳动物内皮细胞的侵入是通过聚集在宿主Arp 2/3复合物上的冗余途径发生的。我们的研究结果揭示了WAVE和Arp 2/3复合物的关键作用，以及比以前在立克次体入侵期间激活的肌动蛋白成核途径中更高程度的变化。
Rickettsiae are obligate intracellular pathogens that are transmitted to humans by arthropod vectors and cause diseases such as spotted fever and typhus. Although rickettsiae require the host cell actin cytoskeleton for invasion, the cytoskeletal proteins that mediate this process have not been completely described. To identify the host factors important during cell invasion by Rickettsia parkeri, a member of the spotted fever group (SFG), we performed an RNAi screen targeting 105 proteins in Drosophila melanogaster S2R+ cells. The screen identified 21 core proteins important for invasion, including the GTPases Rac1 and Rac2, the WAVE nucleation promoting factor complex and the Arp2/3 complex. In mammalian cells, including endothelial cells, the natural targets of R. parkeri, the Arp2/3 complex was also crucial for invasion, while requirements for WAVE2 as well as Rho GTPases depended on the particular cell type. We propose that R. parkeri invades S2R+ arthropod cells through a primary pathway leading to actin nucleation, whereas invasion of mammalian endothelial cells occurs via redundant pathways that converge on the host Arp2/3 complex. Our results reveal a key role for the WAVE and Arp2/3 complexes, as well as a higher degree of variation than previously appreciated in actin nucleation pathways activated during Rickettsia invasion.
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DOI：
10.1038/nrm2867
发表时间：
2010-04
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.7
作者：
Gillespie JJ;Ammerman NC;Dreher-Lesnick SM;Rahman MS;Worley MJ;Setubal JC;Sobral BS;Azad AF
通讯作者：
Azad AF
影响因子：
3.1
作者：
Hybiske, Kevin;Stephens, Richard S.
通讯作者：
Stephens, Richard S.
影响因子：
30.3
作者：
Haenisch, Jan;Koelm, Robert;Stradal, Theresia E. B.
通讯作者：
Stradal, Theresia E. B.
影响因子：
6.7
作者：
Elwell, Cherilyn A.;Ceesay, Alhaji;Kim, Jung Hwa;Kalman, Daniel;Engel, Joanne N.
通讯作者：
Engel, Joanne N.