Analysis of the mechanisms of Salmonella-induced actin assembly during invasion of host cells and intracellular replication
Analysis of the mechanisms of Salmonella-induced actin assembly during invasion of host cells and intracellular replication
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DOI：
10.1111/j.1462-5822.2004.00417.x
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发表时间：
2004-11-01
影响因子：
3.4
通讯作者：
Holden, DW
中科院分区：
文献类型：
--
作者：
Unsworth, KE;Way, M;Holden, DW
鼠伤寒沙门氏菌（S.typhimurium）在入侵宿主细胞期间和细胞内细菌复制过程中诱导肌动蛋白组装。在这项研究中，我们研究了细菌病原体经常利用宿主细胞信号传导途径来操纵真核肌动蛋白细胞骨架的这些过程的参与。我们证实Cdc42、Rac和Arp3参与鼠伤寒沙门氏菌对HeLa细胞的侵袭，并发现N-WASP和Scar/WAVE也在这个过程中发挥作用。然而，我们没有发现这些蛋白质参与细胞内复制过程中肌动蛋白组装的证据。 Cortactin 在入侵和细胞内复制期间被沙门氏菌招募。然而，针对 Cortactin 的 RNA 干扰不会抑制侵袭或细胞内肌动蛋白组装，尽管它导致细胞扩散增加和更多数量的片状伪足。我们还发现 GTPase 动力蛋白或福尔明家族成员 mDia1 在细胞内细菌的肌动蛋白组装中没有任何作用。总的来说，这些数据提供了证据，证明导致 Arp2/3 依赖性肌动蛋白成核的信号通路在鼠伤寒沙门氏菌入侵中发挥重要作用，但不参与细胞内沙门氏菌诱导的肌动蛋白组装，并表明细胞内鼠伤寒沙门氏菌的肌动蛋白组装可能通过一种新机制进行。
Salmonella enterica serovar Typhimurium (S. typhimurium) induces actin assembly both during invasion of host cells and during the course of intracellular bacterial replication. In this study, we investigated the involvement in these processes of host cell signalling pathways that are frequently utilized by bacterial pathogens to manipulate the eukaryotic actin cytoskeleton. We confirmed that Cdc42, Rac, and Arp3 are involved in S. typhimurium invasion of HeLa cells, and found that N-WASP and Scar/WAVE also play a role in this process. However, we found no evidence for the involvement of these proteins in actin assembly during intracellular replication. Cortactin was recruited by Salmonella during both invasion and intracellular replication. However, RNA interference directed against cortactin did not inhibit either invasion or intracellular actin assembly, although it resulted in increased cell spreading and a greater number of lamellipodia. We also found no role for either the GTPase dynamin or the formin family member mDia1 in actin assembly by intracellular bacteria. Collectively, these data provide evidence that signalling pathways leading to Arp2/3-dependent actin nucleation play an important role in S. typhimurium invasion, but are not involved in intracellular Salmonella-induced actin assembly, and suggest that actin assembly by intracellular S. typhimurium may proceed by a novel mechanism.