Shigella IpaD has a dual role: signal transduction from the type III secretion system needle tip and intracellular secretion regulation.

Shigella IpaD has a dual role: signal transduction from the type III secretion system needle tip and intracellular secretion regulation.
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DOI:
10.1111/mmi.12124
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发表时间:
2013-02
影响因子:
3.6
通讯作者:
Martinez-Argudo I
Martinez-Argudo I
中科院分区:
生物学2区
文献类型:
--
作者:
Roehrich AD;Guillossou E;Blocker AJ;Martinez-Argudo I

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III 型分泌系统 (T3SS) 是许多革兰氏阴性细菌与真核细胞相互作用所必需的蛋白质注射装置。虽然志贺氏菌在环境条件适合入侵时组装其 T3SS,但只有在与宿主细胞物理接触后才会激活分泌。首先,分泌易位子以在宿主细胞膜上形成孔,然后是操纵宿主细胞的效应子。分泌激活受到保守的 T3SS 成分的严格控制:针尖蛋白 IpaD 和 IpaB、针本身和细胞内看门蛋白 MxiC。为了进一步表征 IpaD 在激活过程中的作用,我们将随机诱变与遗传筛选相结合,以鉴定无法对宿主细胞接触做出反应的 ipaD 突变株。 II类突变体在分泌诱导方面存在总体缺陷。它们映射到 IpaD 的 C 末端螺旋,并可能影响激活信号的产生或传输。 I 类突变体过早地分泌易位蛋白,并且在激活后 IpaD 分泌方面存在特别缺陷。在 mxiC 中发现了表型相当的突变体。我们发现 IpaD 和 MxiC 在相同的细胞内途径中发挥作用。总之,我们证明 IpaD 具有双重作用,在分泌激活过程中在两个不同的位置发挥作用。
Type III secretion systems (T3SSs) are protein injection devices essential for the interaction of many Gram-negative bacteria with eukaryotic cells. While Shigella assembles its T3SS when the environmental conditions are appropriate for invasion, secretion is only activated after physical contact with a host cell. First, the translocators are secreted to form a pore in the host cell membrane, followed by effectors which manipulate the host cell. Secretion activation is tightly controlled by conserved T3SS components: the needle tip proteins IpaD and IpaB, the needle itself and the intracellular gatekeeper protein MxiC. To further characterize the role of IpaD during activation, we combined random mutagenesis with a genetic screen to identify ipaD mutant strains unable to respond to host cell contact. Class II mutants have an overall defect in secretion induction. They map to IpaD's C-terminal helix and likely affect activation signal generation or transmission. The Class I mutant secretes translocators prematurely and is specifically defective in IpaD secretion upon activation. A phenotypically equivalent mutant was found in mxiC. We show that IpaD and MxiC act in the same intracellular pathway. In summary, we demonstrate that IpaD has a dual role and acts at two distinct locations during secretion activation.
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