The bacterial virulence factor InlC perturbs apical cell junctions and promotes cell-to-cell spread of Listeria.
The bacterial virulence factor InlC perturbs apical cell junctions and promotes cell-to-cell spread of Listeria.
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DOI：
10.1038/ncb1964
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发表时间：
2009-10
影响因子：
21.3
通讯作者：
Ireton, Keith
中科院分区：
文献类型：
--
作者：
Rajabian, Tina;Gavicherla, Balramakrishna;Heisig, Martin;Mueller-Altrock, Stefanie;Goebel, Werner;Gray-Owen, Scott D.;Ireton, Keith
一些致病菌，包括单核增生李斯特菌，利用f -肌动蛋白运动过程在哺乳动物细胞间传播。肌动蛋白“彗星尾巴”推动李斯特菌穿过细胞质，导致含有细菌的膜突起，这些突起被邻近细胞内化。李斯特菌克服皮层张力产生突起的机制尚不清楚。在这里，我们确定了直接调节突起的细菌和宿主蛋白。我们发现极化上皮细胞之间的有效扩散需要分泌李斯特菌毒力蛋白InlC。接下来，我们将哺乳动物接头蛋白Tuba鉴定为InlC的配体。InlC与Tuba的c端SH3结构域结合，通常与人类肌动蛋白调节蛋白N-WASP结合。InlC通过抑制Tuba和N-WASP促进突起的形成，很可能是通过破坏N-WASP与Tuba SH3结构域的结合。已知Tuba和N-WASP控制上皮细胞的顶端连接结构。我们证明，通过抑制Tuba和N-WASP， InlC使紧绷的根尖连接变得松弛。肌球蛋白II抑制剂的实验表明，inlc介导的连接扰动解释了这种细菌蛋白在突起形成中的作用。总之，我们的研究结果表明，InlC通过缓解皮质张力促进细菌传播，从而增强活动细菌将质膜变形为突起的能力。
Several pathogenic bacteria, including Listeria monocytogenes, use an F-actin motility process to spread between mammalian cells. Actin ‘comet tails’ propel Listeria through the cytoplasm, resulting in bacteria-containing membrane protrusions that are internalized by neighboring cells. The mechanism by which Listeria overcomes cortical tension to generate protrusions is unknown. Here, we identify bacterial and host proteins that directly regulate protrusions. We show that efficient spreading between polarized epithelial cells requires the secreted Listeria virulence protein InlC. We next identify the mammalian adaptor protein Tuba as a ligand of InlC. InlC binds to a C-terminal SH3 domain in Tuba, which normally engages the human actin regulatory protein N-WASP. InlC promotes protrusion formation by inhibiting Tuba and N-WASP, most likely by impairing binding of N-WASP to the Tuba SH3 domain. Tuba and N-WASP are known to control the structure of apical junctions in epithelial cells. We demonstrate that, by inhibiting Tuba and N-WASP, InlC makes taut apical junctions become slack. Experiments with myosin II inhibitors indicate that InlC-mediated perturbation of junctions accounts for the role of this bacterial protein in protrusion formation. Collectively, our results suggest that InlC promotes bacterial dissemination by relieving cortical tension, thereby enhancing the ability of motile bacteria to deform the plasma membrane into protrusions.
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影响因子：
56.9
作者：
Straight, AF;Cheung, A;Mitchison, TJ
通讯作者：
Mitchison, TJ
影响因子：
11.4
作者：
Pust, S;Morrison, H;Herrlich, P
通讯作者：
Herrlich, P
影响因子：
64.5
作者：
Co, Carl;Wong, Derek T.;Taunton, Jack
通讯作者：
Taunton, Jack
影响因子：
5.8
作者：
Bierne, H.;Sabet, C.;Cossart, R.
通讯作者：
Cossart, R.
DOI：
10.1083/jcb.146.6.1333
发表时间：
1999-09-20
期刊：
The Journal of cell biology
影响因子：
--
作者：
Robbins JR;Barth AI;Marquis H;de Hostos EL;Nelson WJ;Theriot JA
通讯作者：
Theriot JA