Host endoplasmic reticulum COPII proteins control cell-to-cell spread of the bacterial pathogen Listeria monocytogenes.
Host endoplasmic reticulum COPII proteins control cell-to-cell spread of the bacterial pathogen Listeria monocytogenes.
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宿主的内质网copii蛋白控制细菌病原体单核细胞增生的细胞间传播。
DOI：
10.1111/cmi.12409
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发表时间：
2015-06
影响因子：
3.4
通讯作者：
Ireton K
中科院分区：
文献类型：
--
作者：
Gianfelice A;Le PH;Rigano LA;Saila S;Dowd GC;McDivitt T;Bhattacharya N;Hong W;Stagg SM;Ireton K
单核细胞增生李斯特氏菌是一种食源性病原体，利用肌动蛋白依赖性运动在人体细胞之间传播。细胞间的传播涉及运动细菌形成称为“突起”的质膜衍生结构。在培养的肠细胞中，分泌的李斯特菌蛋白InlC通过结合和抑制人支架蛋白Tuba来促进突起形成。在这里，我们证明突出物是由人类 COPII 成分控制的，这些成分指导内质网的运输。共沉淀实验表明 COPII 蛋白 Sec31A 和 Sec13 直接与 Tuba 中的 Src 同源 3 结构域相互作用。这种相互作用被InlC拮抗。 Sec31A 或 Sec13 的耗尽使缺乏 inlC 的李斯特菌突变体恢复了正常的突起形成，而不影响野生型细菌的传播。 COPII 成分 Sar1 的遗传损伤或用布雷菲德菌素 A 处理细胞会影响突起，类似于 Sec31A 或 Sec13 耗尽。这些发现表明 InlC 缓解了宿主介导的李斯特菌传播限制，否则由 COPII 强加。 Sec31A、Sec13 或 Sar1 或布雷菲德菌素 A 处理的抑制也会扰乱细胞-细胞连接的结构。总的来说，这些发现表明 COPII 在控制李斯特菌传播方面发挥着重要作用。我们认为 COPII 可能通过传递在细胞连接处产生张力的宿主蛋白来发挥作用。
Listeria monocytogenes is a food-borne pathogen that uses actin–dependent motility to spread between human cells. Cell-to-cell spread involves the formation by motile bacteria of plasma membrane-derived structures termed ‘protrusions’. In cultured enterocytes, the secreted Listeria protein InlC promotes protrusion formation by binding and inhibiting the human scaffolding protein Tuba. Here we demonstrate that protrusions are controlled by human COPII components that direct trafficking from the endoplasmic reticulum. Co-precipitation experiments indicated that the COPII proteins Sec31A and Sec13 interact directly with a Src Homology 3 domain in Tuba. This interaction was antagonized by InlC. Depletion of Sec31A or Sec13 restored normal protrusion formation to a Listeria mutant lacking inlC, without affecting spread of wild-type bacteria. Genetic impairment of the COPII component Sar1 or treatment of cells with brefeldin A affected protrusions similarly to Sec31A or Sec13 depletion. These findings indicated that InlC relieves a host-mediated restriction of Listeria spread otherwise imposed by COPII. Inhibition of Sec31A, Sec13, or Sar1 or brefeldin A treatment also perturbed the structure of cell-cell junctions. Collectively, these findings demonstrate an important role for COPII in controlling Listeria spread. We propose that COPII may act by delivering host proteins that generate tension at cell junctions.