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

    2 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 - 2018 Aug 1

    Fingerprint

    Ubiquitination
    Autophagy
    Streptococcus pneumoniae
    Pneumonia
    Polyubiquitin
    Golgi Apparatus
    Streptococcus pneumoniae plY protein
    Ubiquitin-Protein Ligases
    Ubiquitin

    Keywords

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

    ASJC Scopus subject areas

    • Microbiology
    • Immunology
    • Virology

    Cite this

    Molecular mechanisms of Streptococcus pneumoniae-targeted autophagy via pneumolysin, Golgi-resident Rab41, and Nedd4-1-mediated K63-linked ubiquitination. / Ogawa, Michinaga; Matsuda, Ryuta; Takada, Naoki; Tomokiyo, Mikado; Yamamoto, Shouji; Shizukusihi, Sayaka; Yamaji, Toshiyuki; Yoshikawa, Yuko; Yoshida, Mitsutaka; Tanida, Isei; Koike, Masato; Murai, Miyo; Morita, Hidetoshi; Takeyama, Haruko; Ryo, Akihide; Guan, Jun Lin; Yamamoto, Masahiro; Inoue, Jun ichiro; Yanagawa, Toru; Fukuda, Mitsunori; Kawabe, Hiroshi; Ohnishi, Makoto.

    In: Cellular Microbiology, Vol. 20, No. 8, e12846, 01.08.2018.

    Research output: Contribution to journalArticle

    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, JL, Yamamoto, M, Inoue, JI, Yanagawa, T, Fukuda, M, Kawabe, H & Ohnishi, M 2018, 'Molecular mechanisms of Streptococcus pneumoniae-targeted autophagy via pneumolysin, Golgi-resident Rab41, and Nedd4-1-mediated K63-linked ubiquitination', Cellular Microbiology, vol. 20, no. 8, e12846. https://doi.org/10.1111/cmi.12846
    Ogawa, Michinaga ; Matsuda, Ryuta ; Takada, Naoki ; Tomokiyo, Mikado ; Yamamoto, Shouji ; Shizukusihi, Sayaka ; Yamaji, Toshiyuki ; Yoshikawa, Yuko ; Yoshida, Mitsutaka ; Tanida, Isei ; Koike, Masato ; Murai, Miyo ; Morita, Hidetoshi ; Takeyama, Haruko ; Ryo, Akihide ; Guan, Jun Lin ; Yamamoto, Masahiro ; Inoue, Jun ichiro ; Yanagawa, Toru ; Fukuda, Mitsunori ; Kawabe, Hiroshi ; Ohnishi, Makoto. / Molecular mechanisms of Streptococcus pneumoniae-targeted autophagy via pneumolysin, Golgi-resident Rab41, and Nedd4-1-mediated K63-linked ubiquitination. In: Cellular Microbiology. 2018 ; Vol. 20, No. 8.
    @article{cc1dd85d8e554b12b6b1fe7c03645161,
    title = "Molecular mechanisms of Streptococcus pneumoniae-targeted autophagy via pneumolysin, Golgi-resident Rab41, and Nedd4-1-mediated K63-linked ubiquitination",
    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.",
    keywords = "K48- and K63-linked polyUb chain, Nedd4-1, pneumolysin, Rab41 (Rab43), selective autophagy, Streptococcus pneumoniae",
    author = "Michinaga Ogawa and Ryuta Matsuda and Naoki Takada and Mikado Tomokiyo and Shouji Yamamoto and Sayaka Shizukusihi and Toshiyuki Yamaji and Yuko Yoshikawa and Mitsutaka Yoshida and Isei Tanida and Masato Koike and Miyo Murai and Hidetoshi Morita and Haruko Takeyama and Akihide Ryo and Guan, {Jun Lin} and Masahiro Yamamoto and Inoue, {Jun ichiro} and Toru Yanagawa and Mitsunori Fukuda and Hiroshi Kawabe and Makoto Ohnishi",
    year = "2018",
    month = "8",
    day = "1",
    doi = "10.1111/cmi.12846",
    language = "English",
    volume = "20",
    journal = "Cellular Microbiology",
    issn = "1462-5814",
    publisher = "Wiley-Blackwell",
    number = "8",

    }

    TY - JOUR

    T1 - Molecular mechanisms of Streptococcus pneumoniae-targeted autophagy via pneumolysin, Golgi-resident Rab41, and Nedd4-1-mediated K63-linked ubiquitination

    AU - Ogawa, Michinaga

    AU - Matsuda, Ryuta

    AU - Takada, Naoki

    AU - Tomokiyo, Mikado

    AU - Yamamoto, Shouji

    AU - Shizukusihi, Sayaka

    AU - Yamaji, Toshiyuki

    AU - Yoshikawa, Yuko

    AU - Yoshida, Mitsutaka

    AU - Tanida, Isei

    AU - Koike, Masato

    AU - Murai, Miyo

    AU - Morita, Hidetoshi

    AU - Takeyama, Haruko

    AU - Ryo, Akihide

    AU - Guan, Jun Lin

    AU - Yamamoto, Masahiro

    AU - Inoue, Jun ichiro

    AU - Yanagawa, Toru

    AU - Fukuda, Mitsunori

    AU - Kawabe, Hiroshi

    AU - Ohnishi, Makoto

    PY - 2018/8/1

    Y1 - 2018/8/1

    N2 - 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.

    AB - 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.

    KW - K48- and K63-linked polyUb chain

    KW - Nedd4-1

    KW - pneumolysin

    KW - Rab41 (Rab43)

    KW - selective autophagy

    KW - Streptococcus pneumoniae

    UR - http://www.scopus.com/inward/record.url?scp=85049808394&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=85049808394&partnerID=8YFLogxK

    U2 - 10.1111/cmi.12846

    DO - 10.1111/cmi.12846

    M3 - Article

    C2 - 29582580

    AN - SCOPUS:85049808394

    VL - 20

    JO - Cellular Microbiology

    JF - Cellular Microbiology

    SN - 1462-5814

    IS - 8

    M1 - e12846

    ER -