Graduate School of Frontier Biosciences, Osaka University

Japanese

Recruitment of The Autophagic Machinery to Endosomes during Infection is Mediated by Ubiquitin

Journal J Cell Biol (2013)
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Authors Naonobu Fujita (1, 2), Eiji Morita (3), Takashi Itoh (8), Atsushi Tanaka (2), Megumi Nakaoka (2), Yuki Osada (1), Tetsuo Umemoto (2), Tatsuya Saitoh (4, 5), Hitoshi Nakatogawa (7), Shouhei Kobayashi (9), Tokuko Haraguchi (9), Jun-Lin Guan (10), Kazuhiro Iwai (11), Fuminori Tokunaga (12), Kazunobu Saito (6), Koutaro Ishibashi (8), Shizuo Akira (4, 5), Mitsunori Fukuda (8), Takeshi Noda (1, 2) & Tamotsu Yoshimori (1, 2)
  1. Department of Genetics, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
  2. Laboratory of Intracellular Membrane Dynamics, Graduate school of Frontier Biosciences, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
  3. Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
  4. Department of Host Defense, WPI Immunology Frontier Research Center, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
  5. Department of Host Defense, Research Institute for Microbial Disease, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
  6. Core Instrumentation Facility, Research Institute for Microbial Disease, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
  7. Frontier Research Center, Tokyo Institute of Technology, Yokohama 226-8503, Japan
  8. Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi 980-8578, Japan
  9. Advance ICT Research Institute Kobe, National Institute of Information and Communications Technology, Kobe 651-2492, Japan
  10. Department of Internal Medicine–MMG, University of Michigan Medical School, Ann Arbor, MI 48109
  11. Department of Molecular and Cellular Physiology, Graduate School of Medicine, Kyoto University, Yoshida-konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
  12. Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-machi, Maebashi, Gunma 371-8512, Japan
Title Recruitment of The Autophagic Machinery 1 to Endosomes during Infection is Mediated by Ubiquitin
Laboratory Laboratory of Intracellular Membrane Dynamics 〈Prof. Yoshimori〉
Abstract Although ubiquitin is thought to be important for the autophagic sequestration of invading bacteria (also called xenophagy), its precise role remains largely enigmatic. Here we determined how ubiquitin is involved in this process. Following invasion, ubiquitin is conjugated to host cellular proteins in endosomes that contain *Salmonella* or transfection reagent-coated latex (polystyrene) beads, which mimic invading bacteria. Ubiquitin is recognized by the autophagic machinery independently of the LC3-ubiquitin interaction through adaptor proteins, including a direct interaction between ubiquitin and Atg16L1. To ensure that invading pathogens are captured and degraded, Atg16L1 targeting is secured by two backup systems that anchor Atg16L1 to ubiquitin-decorated endosomes. Thus, we reveal that ubiquitin is a pivotal molecule that connects bacteria-containing endosomes with the autophagic machinery upstream of LC3.