Listeria monocytogenes ActA-mediated escape from autophagic recognition
Listeria monocytogenes ActA-mediated escape from autophagic recognition
复制标题
DOI：
10.1038/ncb1967
复制
发表时间：
2009-10-01
影响因子：
21.3
通讯作者：
Sasakawa, Chihiro
中科院分区：
文献类型：
--
作者：
Yoshikawa, Yuko;Ogawa, Michinaga;Sasakawa, Chihiro
自噬降解不必要的细胞器和错误折叠的蛋白质聚集体（1），以及侵入细胞质的细菌（2）。然而，细菌单核细胞增生李斯特菌有效地逃避自噬（3，4）。在这里，我们表明，招聘的Arp 2/3复合物和Ena/VASP，通过细菌ActA蛋白，细菌表面伪装的自噬识别，一种活动，是独立的能力，介导细菌运动的细菌。L.表达缺乏募集宿主蛋白能力的ActA突变体的单核细胞增多症最初经历泛素化，随后是p62（也称为SQSTM 1）和LC 3的募集，最后经历自噬。ActA介导泛素化保护的能力通过产生聚集倾向的GFP-ActA-Q79 C和GFP ActA-170* 嵌合体进一步证明，所述嵌合体由GFP（绿色荧光蛋白）、ActA蛋白和polyQ（5）或高尔基体膜蛋白GCP 170的片段组成（参考文献6）。GFP-ActA-Q79 C和GFP-ActA-170* 在宿主细胞质中形成聚集体，然而，这些含有ActA的聚集体不被靶向与泛素和p62缔合。我们的研究结果表明，ActA介导的宿主蛋白募集是一种独特的细菌伪装策略，以逃避自噬。
Autophagy degrades unnecessary organelles and misfolded protein aggregates(1), as well as cytoplasm-invading bacteria(2). Nevertheless, the bacteria Listeria monocytogenes efficiently escapes autophagy(3,4). We show here that recruitment of the Arp2/3 complex and Ena/VASP, via the bacterial ActA protein, to the bacterial surface disguises the bacteria from autophagic recognition, an activity that is independent of the ability to mediate bacterial motility. L. monocytogenes expressing ActA mutants that lack the ability to recruit the host proteins initially underwent ubiquitylation, followed by recruitment of p62 (also known as SQSTM1) and LC3, before finally undergoing autophagy. The ability of ActA to mediate protection from ubiquitylation was further demonstrated by generating aggregate-prone GFP-ActA-Q79C and GFP ActA-170* chimaeras, consisting of GFP (green fluorescent protein), the ActA protein and segments of polyQ(5) or Golgi membrane protein GCP170 (ref. 6). GFP-ActA-Q79C and GFP-ActA-170* formed aggregates in the host cell cytoplasm, however, these ActA-containing aggregates were not targeted for association with ubiquitin and p62. Our findings indicate that ActA-mediated host protein recruitment is a unique bacterial disguise tactic to escape from autophagy.