Activation of a RhoA/Myosin II-Dependent but Arp2/3 Complex-Independent Pathway Facilitates Salmonella Invasion
Activation of a RhoA/Myosin II-Dependent but Arp2/3 Complex-Independent Pathway Facilitates Salmonella Invasion
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DOI：
10.1016/j.chom.2011.03.009
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发表时间：
2011-04-21
影响因子：
30.3
通讯作者：
Stradal, Theresia E. B.
中科院分区：
文献类型：
--
作者：
Haenisch, Jan;Koelm, Robert;Stradal, Theresia E. B.
沙门氏菌通过病原体的第三型分泌系统(T3SS)转位的毒力效应分子刺激宿主细胞的入侵。这些因子操纵宿主信号通路，主要由Rho家族GTP酶驱动，最终依赖Arp2/3复合体激活宿主肌动蛋白核，介导沙门氏菌进入宿主细胞。然而，最近的数据表明，在依赖T3SS的沙门氏菌入侵过程中存在其他协同作用的机制。我们确定了肌球蛋白II介导的机制，该机制独立于Arp2/3依赖的途径，但与Arp2/3依赖的途径互补，有助于沙门氏菌入侵非吞噬细胞。我们还证实，T3SS效应器SopB构成了Rho/Rho激酶和肌球蛋白II依赖的侵袭途径的重要调节因子。因此，沙门氏菌通过操纵宿主内基于肌动蛋白的两个核心机制进入非吞噬细胞：Arp2/3复合体驱动的肌动蛋白聚合和肌动蛋白介导的收缩。
Salmonella stimulates host cell invasion using virulence effectors translocated by the pathogen's type-three secretion system (T3SS). These factors manipulate host signaling pathways, primarily driven by Rho family GTPases, which culminates in Arp2/3 complex-dependent activation of host actin nucleation to mediate the uptake of Salmonella into host cells. However, recent data argue for the existence of additional mechanisms that cooperate in T3SS-dependent Salmonella invasion. We identify a myosin II-mediated mechanism, operating independent of but complementary to the Arp2/3-dependent pathway, as contributing to Salmonella invasion into nonphagocytic cells. We also establish that the T3SS effector SopB constitutes an important regulator of this Rho/Rho kinase and myosin II-dependent invasion pathway. Thus, Salmonella enters nonphagocytic cells by manipulating the two core machineries of actin-based motility in the host: Arp2/3 complex-driven actin polymerization and actomyosin-mediated contractility.