Molecular mechanisms of Streptococcus pneumoniae-targeted autophagy via pneumolysin, Golgi-resident Rab41, and Nedd4-1-mediated K63-linked ubiquitination

Michinaga Ogawa, Ryuta Matsuda, Naoki Takada, Mikado Tomokiyo, Shouji Yamamoto, Sayaka Shizukusihi, Toshiyuki Yamaji, Yuko Yoshikawa, Mitsutaka Yoshida, Isei Tanida, Masato Koike, Miyo Murai, Hidetoshi Morita, Haruko Takeyama, Akihide Ryo, Jun Lin Guan, Masahiro Yamamoto, Jun ichiro Inoue, Toru Yanagawa, Mitsunori FukudaHiroshi Kawabe, Makoto Ohnishi

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Streptococcus pneumoniae is the most common causative agent of community-acquired pneumonia and can penetrate epithelial barriers to enter the bloodstream and brain. We investigated intracellular fates of S. pneumoniae and found that the pathogen is entrapped by selective autophagy in pneumolysin- and ubiquitin-p62-LC3 cargo-dependent manners. Importantly, following induction of autophagy, Rab41 was relocated from the Golgi apparatus to S. pneumoniae-containing autophagic vesicles (PcAV), which were only formed in the presence of Rab41-positive intact Golgi apparatuses. Moreover, subsequent localization and regulation of K48- and K63-linked polyubiquitin chains in and on PcAV were clearly distinguishable from each other. Finally, we found that E3 ligase Nedd4-1 was recruited to PcAV and played a pivotal role in K63-linked polyubiquitin chain (K63Ub) generation on PcAV, promotion of PcAV formation, and elimination of intracellular S. pneumoniae. These findings suggest that Nedd4-1-mediated K63Ub deposition on PcAV acts as a scaffold for PcAV biogenesis and efficient elimination of host cell-invaded pneumococci.

Original languageEnglish
Article numbere12846
JournalCellular Microbiology
Volume20
Issue number8
DOIs
Publication statusPublished - Aug 2018

Keywords

  • K48- and K63-linked polyUb chain
  • Nedd4-1
  • Rab41 (Rab43)
  • Streptococcus pneumoniae
  • pneumolysin
  • selective autophagy

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Virology

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  • Cite this

    Ogawa, M., Matsuda, R., Takada, N., Tomokiyo, M., Yamamoto, S., Shizukusihi, S., Yamaji, T., Yoshikawa, Y., Yoshida, M., Tanida, I., Koike, M., Murai, M., Morita, H., Takeyama, H., Ryo, A., Guan, J. L., Yamamoto, M., Inoue, J. I., Yanagawa, T., ... Ohnishi, M. (2018). Molecular mechanisms of Streptococcus pneumoniae-targeted autophagy via pneumolysin, Golgi-resident Rab41, and Nedd4-1-mediated K63-linked ubiquitination. Cellular Microbiology, 20(8), [e12846]. https://doi.org/10.1111/cmi.12846