Molecular mechanism of protrusion formation during cell-to-cell spread of Listeria.
Molecular mechanism of protrusion formation during cell-to-cell spread of Listeria.
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DOI：
10.3389/fcimb.2014.00021
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发表时间：
2014
影响因子：
5.7
通讯作者：
Schubert WD
中科院分区：
文献类型：
--
作者：
Ireton K;Rigano LA;Polle L;Schubert WD
细菌病原体单核细胞增多性李斯特菌使用依赖于宿主肌动蛋白细胞骨架的运动过程在人体组织内传播。细胞间传播涉及能动细菌将宿主质膜重塑成突起的能力，突起被邻近细胞内化。最近的结果表明，李斯特菌突起在极化的人类细胞中的形成涉及由支架蛋白Tuba及其效应物N-WASP和Cdc 42组成的宿主信号传导途径的细菌拮抗作用。这三种人类蛋白质形成复合物，在顶端细胞连接处产生张力。李斯特菌通过分泌一种名为InlC的蛋白质来缓解这种张力并促进突起的形成。InlC与Tuba中的Src同源3（SH 3）结构域相互作用，从而从该结构域置换N-WASP。InlC与Tuba的相互作用是李斯特菌在培养的人细胞和感染的动物中有效传播所必需的。最近的结构数据已经阐明了InlC/Tuba相互作用的机制细节，揭示了InlC和N-WASP竞争Tuba SH 3结构域中部分重叠的结合表面。InlC以比N-WASP更高的亲和力结合该结构域，解释了InlC如何能够破坏Tuba/N-WASP复合物。
The bacterial pathogen Listeria monocytogenes spreads within human tissues using a motility process dependent on the host actin cytoskeleton. Cell-to-cell spread involves the ability of motile bacteria to remodel the host plasma membrane into protrusions, which are internalized by neighboring cells. Recent results indicate that formation of Listeria protrusions in polarized human cells involves bacterial antagonism of a host signaling pathway comprised of the scaffolding protein Tuba and its effectors N-WASP and Cdc42. These three human proteins form a complex that generates tension at apical cell junctions. Listeria relieves this tension and facilitates protrusion formation by secreting a protein called InlC. InlC interacts with a Src Homology 3 (SH3) domain in Tuba, thereby displacing N-WASP from this domain. Interaction of InlC with Tuba is needed for efficient Listeria spread in cultured human cells and infected animals. Recent structural data has elucidated the mechanistic details of InlC/Tuba interaction, revealing that InlC and N-WASP compete for partly overlapping binding surfaces in the Tuba SH3 domain. InlC binds this domain with higher affinity than N-WASP, explaining how InlC is able to disrupt Tuba/N-WASP complexes.
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影响因子：
3.3
作者：
Kodani, Andrew;Kristensen, Irene;Suetterlin, Christine
通讯作者：
Suetterlin, Christine
影响因子：
3.4
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