Legionella pneumophila regulates host cell motility by targeting Phldb2 with a 14-3-3ζ-dependent protease effector

  1. Lei Song  Is a corresponding author
  2. Jingjing Luo
  3. Hongou Wang
  4. Dan Huang
  5. Yunhao Tan
  6. Yao Liu
  7. Yingwu Wang
  8. Kaiwen Yu
  9. Yong Zhang
  10. Xiaoyun Liu
  11. Dan Li  Is a corresponding author
  12. Zhao-Qing Luo  Is a corresponding author
  1. Jilin University, China
  2. Peking University Health Science Center, China
  3. Purdue University, United States

Abstract

The cytoskeleton network of eukaryotic cells is essential for diverse cellular processes, including vesicle trafficking, cell motility and immunity, thus is a common target for bacterial virulence factors. A number of effectors from the bacterial pathogen Legionella pneumophila have been shown to modulate the function of host actin cytoskeleton to construct the Legionella-containing vacuole (LCV) permissive for its intracellular replication. In this study, we found that the Dot/Icm effector Lem8 (Lpg1290) is a protease whose activity is catalyzed by a Cys-His-Asp motif known to be associated with diverse biochemical activities. Intriguingly, we found that Lem8 interacts with the host regulatory protein 14-3-3ζ, which activates its protease activity. Furthermore, Lem8 undergoes self-cleavage in a process that requires 14-3-3ζ. We identified the Pleckstrin homology-like domain-containing protein Phldb2 involved in cytoskeleton organization as a target of Lem8 and demonstrated that Lem8 plays a role in the inhibition of host cell migration by attacking Phldb2.

Data availability

All data generated or analysed during this study are included in the manuscript. Files for original images of blots and gels prior to being cropped for use in the main text have been included in the Supporting file (zip format).

Article and author information

Author details

  1. Lei Song

    Department of Respiratory Medicine, Jilin University, Changchun, China
    For correspondence
    lsong@jlu.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4115-065X
  2. Jingjing Luo

    Department of Respiratory Medicine, Jilin University, Changchun, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Hongou Wang

    Department of Microbiology, Peking University Health Science Center, Peking, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Dan Huang

    Department of Respiratory Medicine, Jilin University, Changchun, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Yunhao Tan

    Department of Biological Sciences, Purdue University, West Lafayette, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Yao Liu

    Department of Biological Sciences, Purdue University, West Lafayette, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4330-2389
  7. Yingwu Wang

    Department of Respiratory Medicine, Jilin University, Changchun, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Kaiwen Yu

    Department of Microbiology, Peking University Health Science Center, Peking, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6050-8477
  9. Yong Zhang

    Department of Respiratory Medicine, Jilin University, Changchun, China
    Competing interests
    The authors declare that no competing interests exist.
  10. Xiaoyun Liu

    Department of Microbiology, Peking University Health Science Center, Peking, China
    Competing interests
    The authors declare that no competing interests exist.
  11. Dan Li

    Department of Respiratory Medicine, Jilin University, Changchun, China
    For correspondence
    li_dan@jlu.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
  12. Zhao-Qing Luo

    Department of Biological Science, Purdue University, West Lafayette, United States
    For correspondence
    luoz@purdue.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8890-6621

Funding

Jilin Scientific and Technological Development Program (20200403117SF)

  • Lei Song

Jilin Scientific and Technological Development Program (20200901010SF)

  • Dan Li

National Natural Science Foundation of China (21974002)

  • Xiaoyun Liu

Beijing Municipal Natural Science Foundation (5202012)

  • Xiaoyun Liu

National Institutes of Health (R01AI127465)

  • Zhao-Qing Luo

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Christina L Stallings, Washington University School of Medicine, United States

Publication history

  1. Received: August 20, 2021
  2. Preprint posted: September 6, 2021 (view preprint)
  3. Accepted: February 16, 2022
  4. Accepted Manuscript published: February 17, 2022 (version 1)
  5. Version of Record published: February 24, 2022 (version 2)

Copyright

© 2022, Song et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Lei Song
  2. Jingjing Luo
  3. Hongou Wang
  4. Dan Huang
  5. Yunhao Tan
  6. Yao Liu
  7. Yingwu Wang
  8. Kaiwen Yu
  9. Yong Zhang
  10. Xiaoyun Liu
  11. Dan Li
  12. Zhao-Qing Luo
(2022)
Legionella pneumophila regulates host cell motility by targeting Phldb2 with a 14-3-3ζ-dependent protease effector
eLife 11:e73220.
https://doi.org/10.7554/eLife.73220

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