Golgi-Resident GTPase Rab30 Promotes the Biogenesis of Pathogen-Containing Autophagosomes

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.自噬（Autophagy）作为宿主防御系统，可对抗A群链球菌（Group A Streptococcus, GAS）这类病原微生物。自噬是一种由膜介导的降解系统，其调控依赖于胞内膜运输调控因子，包括小GTP酶Rab蛋白（small GTPase Rab proteins）。本研究鉴定出Rab30是含GAS的自噬体样液泡（autophagosome-like vacuoles, GcAVs）的新型调控因子。我们发现，作为高尔基体驻留Rab蛋白的Rab30，会在上皮细胞受GAS感染诱导自噬时，被招募至GcAVs中。Rab30的招募依赖于其GTP酶活性。此外，敲低Rab30的表达会显著降低GcAV的形成效率，并削弱胞内GAS的降解能力。Rab30通常的功能是维持高尔基体的结构完整性，但即便高尔基体被破坏，GcAV的形成仍可发生。尽管Rab30也会与饥饿诱导的自噬体共定位，但饥饿状态下自噬体的形成并不依赖Rab30。上述结果表明，Rab30介导抗GAS的自噬过程，与其在维持高尔基体结构完整性中的常规细胞功能相互独立；且细菌感染过程中的自噬体生物发生涉及特定的Rab GTP酶。