Striking a balance:: Modulation of the actin cytoskeleton by Salmonella
Striking a balance:: Modulation of the actin cytoskeleton by Salmonella
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DOI：
10.1073/pnas.97.16.8754
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发表时间：
2000-08-01
影响因子：
11.1
通讯作者：
Zhou, D
中科院分区：
文献类型：
--
作者：
Galán, JE;Zhou, D
沙门氏菌属已经进化出进入通常非吞噬细胞的能力。内化过程是细菌和宿主细胞之间显着相互作用的结果。接触后，沙门氏菌立即通过称为 III 型分泌系统的特殊细胞器的功能将许多细菌效应蛋白递送到宿主细胞胞浆中。最初，两种递送的蛋白 SopE 和 SopB 刺激小 GTP 结合蛋白 Cdc42 和 Rac。 SopE 是这些 GTP 酶的交换因子，SopB 是肌醇多磷酸磷酸酶。 Cdc42 和 Rac 的刺激会导致显着的肌动蛋白细胞骨架重排，SipA 会进一步增强这种重排，SipA 是一种沙门氏菌蛋白，也通过 III 型分泌系统递送到宿主细胞中，SipA 降低了 C-肌动蛋白的临界浓度，稳定了细菌进入位点的 F-肌动蛋白，并增加了宿主细胞蛋白 T-plastin（纤毛蛋白）的成束活性。沙门氏菌刺激的细胞反应是短暂的；因此，细菌进入后，细胞立即恢复其正常结构。值得注意的是，这一过程是由 III 型分泌系统的另一个靶标 SptP 介导的，SptP 通过充当 Cdc42 和 Rac 的 GTPase 激活蛋白来发挥其功能，在细菌效应子 SopE 和 SopB 刺激后关闭这些 G 蛋白。沙门氏菌与宿主细胞的平衡相互作用是病原体/宿主关系复杂性的一个显着例子，这种关系是通过长期共存的进化形成的。
Salmonella spp. have evolved the ability to enter into cells that are normally nonphagocytic. The internalization process is the result of a remarkable interaction between the bacteria and the host cells. Immediately on contact, Salmonella delivers a number of bacterial effector proteins into the host cell cytosol through the function of a specialized organelle termed the type III secretion system. Initially, two of the delivered proteins, SopE and SopB, stimulate the small GTP-binding proteins Cdc42 and Rac. SopE is an exchange factor for these GTPases, and SopB is an inositol polyphosphate phosphatase. Stimulation of Cdc42 and Rac leads to marked actin cytoskeleton rearrangements, which are further enhanced by SipA, a Salmonella protein also delivered into the host cell by the type III secretion system, SipA lowers the critical concentration of C-actin, stabilizes F-actin at the site of bacterial entry, and increases the bundling activity of the host-cell protein T-plastin (fimbrin). The cellular responses stimulated by Salmonella are short-lived; therefore, immediately after bacterial entry, the cell regains its normal architecture, Remarkably, this process is mediated by SptP, another target of the type III secretion system, SptP exert its function by serving as a GTPase-activating protein for Cdc42 and Rac, turning these G proteins off after their stimulation by the bacterial effecters SopE and SopB. The balanced interaction of Salmonella with host cells constitutes a remarkable example of the sophisticated nature of a pathogen/host relationship shaped by evolution through a longstanding coexistence.