title: The small GTPases Rab9A and Rab23 function at distinct steps in autophagy during Group A Streptococcus infection.
abstract: Autophagy mediates the degradation of cytoplasmic contents in the lysosome and plays a significant role in immunity. Here we identified the small GTPases Rab9A and Rab23 as novel autophagy regulators during Group A streptococcus (GAS) infection. Rab9A was recruited to GAS-containing autophagosome-like vacuoles (GcAVs) after autophagosomal maturation and its activity was required for GcAV enlargement and eventual lysosomal fusion. GcAV enlargement appeared to be related to homotypic fusion of GcAVs with Rab9A. Rab23 was recruited to GAS-capturing forming autophagosomes. Knockdown of Rab23 expression decreased both LC3- and Atg5-positive GAS formation and caused the accumulation of LC3-positive structures that did not associate with intracellular GAS. It was suggested, therefore, that Rab23 is required for GcAV formation and is involved in GAS targeting of autophagic vacuoles. Furthermore, knockdown of Rab9A or Rab23 expression impaired the degradation of intracellular GAS. Therefore, our data reveal that the Rab9A and Rab23 GTPases play crucial roles in autophagy of GAS. However, neither Rab9A nor Rab23 were localized to starvation-induced autophagosomes. Not only Rab9A but also Rab23 was dispensable for starvation-induced autophagosome formation. These findings demonstrate that specific Rab proteins function at distinct steps during autophagy in response to GAS infection.
authors.affiliation: Section of Bacterial Pathogenesis, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nozawa
authors.forename: Chihiro
authors.initials: C
authors.lastname: Aikawa
authors.forename: Akira
authors.initials: A
authors.lastname: Goda
authors.forename: Fumito
authors.initials: F
authors.lastname: Maruyama
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Hamada
authors.forename: Ichiro
authors.initials: I
authors.lastname: Nakagawa
mesh_terms: D001343:Autophagy; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D008247:Lysosomes / Q000201:enzymology / Q000382:microbiology; D008561:Membrane Fusion; D050296:Microbial Viability; D018613:Microscopy, Confocal; D010588:Phagosomes / Q000201:enzymology / Q000382:microbiology; D021381:Protein Transport; D034622:RNA Interference; D013290:Streptococcal Infections / Q000382:microbiology*; D013297:Streptococcus pyogenes / Q000502:physiology*; D014617:Vacuoles / Q000201:enzymology; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
chemical_list: C486614:RAB23 protein, human; C079856:RAB9A protein, human; D020691:rab GTP-Binding Proteins