Open AccessMolecular mechanisms of Streptococcus pneumoniae ‐targeted autophagy via pneumolysin, Golgi‐resident Rab41, and Nedd4‐1‐mediated K63‐linked ubiquitination
Author(s) -
Ogawa Michinaga,
Matsuda Ryuta,
Takada Naoki,
Tomokiyo Mikado,
Yamamoto Shouji,
Shizukuishi Sayaka,
Yamaji Toshiyuki,
Yoshikawa Yuko,
Yoshida Mitsutaka,
Tanida Isei,
Koike Masato,
Murai Miyo,
Morita Hidetoshi,
Takeyama Haruko,
Ryo Akihide,
Guan JunLin,
Yamamoto Masahiro,
Inoue Junichiro,
Yanagawa Toru,
Fukuda Mitsunori,
Kawabe Hiroshi,
Ohnishi Makoto
Publication year - 2018
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/cmi.12846
Subject(s) - pneumolysin , autophagy , biology , streptococcus pneumoniae , ubiquitin , microbiology and biotechnology , intracellular , golgi apparatus , nedd4 , biogenesis , endosome , ubiquitin ligase , inflammasome , gene , apoptosis , biochemistry , receptor , endoplasmic reticulum , antibiotics
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.