Golgi-Resident GTPase Rab30 Promotes the Biogenesis of Pathogen-Containing Autophagosomes.
Golgi-Resident GTPase Rab30 Promotes the Biogenesis of Pathogen-Containing Autophagosomes.
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DOI：
10.1371/journal.pone.0147061
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Nakagawa I
中科院分区：
文献类型：
--
作者：
Oda S;Nozawa T;Nozawa-Minowa A;Tanaka M;Aikawa C;Harada H;Nakagawa I
自噬是一种宿主防御系统，可抵抗a群链球菌等病原微生物。自噬是一种膜介导的降解系统，受细胞膜内运输调节剂的调节，包括小的GTPase Rab蛋白。在这里，我们发现Rab30是一种新的含有gas的自噬体样液泡（gcav）调节剂。我们发现Rab30，一个高尔基居住Rab，被招募到gcav响应自噬诱导的上皮细胞的GAS感染。Rab30的招募依赖于其GTPase活性。此外，Rab30表达的下调显著降低了GcAV的形成效率，破坏了细胞内GAS的降解。Rab30的正常功能是维持高尔基复合体的结构完整性，但即使高尔基体被破坏，GcAV的形成也会发生。虽然Rab30也与饥饿诱导的自噬体共定位，但在饥饿期间自噬体的形成并不需要Rab30。这些结果表明，Rab30介导GAS的自噬独立于其在高尔基体结构维持中的正常细胞作用，并且细菌感染期间自噬体的生物发生涉及特异性的Rab gtpase。
Autophagy acts as a host-defense system against pathogenic microorganisms such as Group A Streptococcus (GAS). Autophagy is a membrane-mediated degradation system that is regulated by intracellular membrane trafficking regulators, including small GTPase Rab proteins. Here, we identified Rab30 as a novel regulator of GAS-containing autophagosome-like vacuoles (GcAVs). We found that Rab30, a Golgi-resident Rab, was recruited to GcAVs in response to autophagy induction by GAS infection in epithelial cells. Rab30 recruitment was dependent upon its GTPase activity. In addition, the knockdown of Rab30 expression significantly reduced GcAV formation efficiency and impaired intracellular GAS degradation. Rab30 normally functions to maintain the structural integrity of the Golgi complex, but GcAV formation occurred even when the Golgi apparatus was disrupted. Although Rab30 also colocalized with a starvation-induced autophagosome, Rab30 was not required for autophagosome formation during starvation. These results suggest that Rab30 mediates autophagy against GAS independently of its normal cellular role in the structural maintenance of the Golgi apparatus, and autophagosome biogenesis during bacterial infection involves specific Rab GTPases.