Bacterial actin assembly requires Toca-1 to relieve N-WASP autoinhibition
Bacterial actin assembly requires Toca-1 to relieve N-WASP autoinhibition
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DOI：
10.1016/j.chom.2007.10.011
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发表时间：
2008-01-01
影响因子：
30.3
通讯作者：
Goldberg, Marcia B.
中科院分区：
文献类型：
--
作者：
Leung, Yiuka;Ally, Shabeen;Goldberg, Marcia B.
哺乳动物细胞质中的肌动蛋白聚合可以通过解除 N-WASP 自身抑制状态的机制局部激活，N-WASP 是肌动蛋白组装的启动子，这一过程也需要 Toca-1 蛋白。包括志贺氏菌在内的几种致病细菌利用这种宿主特征来有效地感染和传播。志贺氏菌外膜蛋白 IcsA 招募 N-WASP，其在细菌表面激活后介导局部肌动蛋白聚合。在完整哺乳动物细胞的生理或病理肌动蛋白组装过程中，Toca-1 在 N-WASP 激活中的分子作用仍不清楚。我们表明，福氏链霉启动肌动蛋白尾部需要 Toca-1 将 N-WASP 从封闭的非活性构象转变为开放的活性构象。虽然 N-WASP 募集依赖于 IcsA，但 Toca-1 募集却由福氏链霉 III 型分泌效应子介导。因此，弗氏链霉菌独立劫持 N-WASP 肌动蛋白组装途径的两个节点，以启动局部肌动蛋白尾部组装。
Actin polymerization in the mammalian cytosol can be locally activated by mechanisms that relieve the autoinhibited state of N-WASP, an initiator of actin assembly, a process that also requires the protein Toca-1. Several pathogenic bacteria, including Shigella, exploit this host feature to infect and disseminate efficiently. The Shigella outer membrane protein IcsA recruits N-WASP, which upon activation at the bacterial surface mediates localized actin polymerization. The molecular role of Toca-1 in N-WASP activation during physiological or pathological actin assembly processes in intact mammalian cells remains unclear. We show that actin tail initiation by S. flexneri requires Toca-1 for the conversion of N-WASP from a closed inactive conformation to an open active one. While N-WASP recruitment is dependent on IcsA, Toca-1 recruitment is instead mediated by S. flexneri type III secretion effectors. Thus, S. flexneri independently hijacks two nodes of the N-WASP actin assembly pathway to initiate localized actin tail assembly.