title: Rab17-mediated recycling endosomes contribute to autophagosome formation in response to Group A Streptococcus invasion.
abstract: Autophagy plays a crucial role in host defence by facilitating the degradation of invading bacteria such as Group A Streptococcus (GAS). GAS-containing autophagosome-like vacuoles (GcAVs) form when GAS-targeting autophagic membranes entrap invading bacteria. However, the membrane origin and the precise molecular mechanism that underlies GcAV formation remain unclear. In this study, we found that Rab17 mediates the supply of membrane from recycling endosomes (REs) to GcAVs. We showed that GcAVs contain the RE marker transferrin receptor (TfR). Colocalization analyses demonstrated that Rab17 colocalized effectively with GcAV. Rab17 and TfR were visible as punctate structures attached to GcAVs and the Rab17-positive dots were recruited to the GAS-capturing membrane. Overexpression of Rab17 increased the TfR-positive GcAV content, whereas expression of the dominant-negative Rab17 form (Rab17 N132I) caused a decrease, thereby suggesting the involvement of Rab17 in RE-GcAV fusion. The efficiency of GcAV formation was lower in Rab17 N132I-overexpressing cells. Furthermore, knockdown of Rabex-5, the upstream activator of Rab17, reduced the GcAV formation efficiency. These results suggest that Rab17 and Rab17-mediated REs are involved in GcAV formation. This newly identified function of Rab17 in supplying membrane from REs to GcAVs demonstrates that RE functions as a primary membrane source during antibacterial autophagy.
authors: 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: Bijaya
authors: B
authors: Haobam
authors: Takashi
authors: T
authors: Nozawa
authors: Atsuko
authors: A
authors: Minowa-Nozawa
authors: Misako
authors: M
authors: Tanaka
authors: Seiichiro
authors: S
authors: Oda
authors: Takayasu
authors: T
authors: Watanabe
authors: Chihiro
authors: C
authors: Aikawa
authors: Fumito
authors: F
authors: Maruyama
authors: Ichiro
authors: I
authors: Nakagawa
mesh_terms: D001343:Autophagy; D011992:Endosomes / Q000378:metabolism*; D004847:Epithelial Cells / Q000276:immunology* / Q000382:microbiology*; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D010588:Phagosomes / Q000378:metabolism*; D013297:Streptococcus pyogenes / Q000254:growth & development* / Q000276:immunology; D020691:rab GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D020662:Guanine Nucleotide Exchange Factors; C108382:RABGEF1 protein, human; C081073:rab17 protein, epithelial; D020691:rab GTP-Binding Proteins