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Rab41-mediated ESCRT machinery repairs membrane rupture by a bacterial toxin in xenophagy

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  • Takashi Nozawa

    (Kyoto University, Yoshida-Konoe-cho, Sakyo-ku)

  • Hirotaka Toh

    (Kyoto University, Yoshida-Konoe-cho, Sakyo-ku)

  • Junpei Iibushi

    (Kyoto University, Yoshida-Konoe-cho, Sakyo-ku)

  • Kohei Kogai

    (Kyoto University, Yoshida-Konoe-cho, Sakyo-ku)

  • Atsuko Minowa-Nozawa

    (Kyoto University, Yoshida-Konoe-cho, Sakyo-ku)

  • Junko Satoh

    (Kyoto University, Yoshida-Konoe-cho, Sakyo-ku)

  • Shinji Ito

    (Kyoto University, Yoshida-Konoe-cho, Sakyo-ku)

  • Kazunori Murase

    (Kyoto University, Yoshida-Konoe-cho, Sakyo-ku)

  • Ichiro Nakagawa

    (Kyoto University, Yoshida-Konoe-cho, Sakyo-ku)

Abstract

Xenophagy, a type of selective autophagy, is a bactericidal membrane trafficking that targets cytosolic bacterial pathogens, but the membrane homeostatic system to cope with bacterial infection in xenophagy is not known. Here, we show that the endosomal sorting complexes required for transport (ESCRT) machinery is needed to maintain homeostasis of xenophagolysosomes damaged by a bacterial toxin, which is regulated through the TOM1L2–Rab41 pathway that recruits AAA-ATPase VPS4. We screened Rab GTPases and identified Rab41 as critical for maintaining the acidification of xenophagolysosomes. Confocal microscopy revealed that ESCRT components were recruited to the entire xenophagolysosome, and this recruitment was inhibited by intrabody expression against bacterial cytolysin, indicating that ESCRT targets xenophagolysosomes in response to a bacterial toxin. Rab41 translocates to damaged autophagic membranes via adaptor protein TOM1L2 and recruits VPS4 to complete ESCRT-mediated membrane repair in a unique GTPase-independent manner. Finally, we demonstrate that the TOM1L2–Rab41 pathway-mediated ESCRT is critical for the efficient clearance of bacteria through xenophagy.

Suggested Citation

  • Takashi Nozawa & Hirotaka Toh & Junpei Iibushi & Kohei Kogai & Atsuko Minowa-Nozawa & Junko Satoh & Shinji Ito & Kazunori Murase & Ichiro Nakagawa, 2023. "Rab41-mediated ESCRT machinery repairs membrane rupture by a bacterial toxin in xenophagy," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42039-2
    DOI: 10.1038/s41467-023-42039-2
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    References listed on IDEAS

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    1. Hiroyuki Kabayama & Makoto Takeuchi & Naoko Tokushige & Shin-ichi Muramatsu & Miyuki Kabayama & Mitsunori Fukuda & Yoshiyuki Yamada & Katsuhiko Mikoshiba, 2020. "An ultra-stable cytoplasmic antibody engineered for in vivo applications," Nature Communications, Nature, vol. 11(1), pages 1-20, December.
    2. Yoshinori Takahashi & Haiyan He & Zhenyuan Tang & Tatsuya Hattori & Ying Liu & Megan M. Young & Jacob M. Serfass & Longgui Chen & Melat Gebru & Chong Chen & Carson A. Wills & Jennifer M. Atkinson & Ha, 2018. "An autophagy assay reveals the ESCRT-III component CHMP2A as a regulator of phagophore closure," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
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