Legionella pneumophila regulates host cell motility by targeting Phldb2 with a 14-3-3ζ-dependent protease effector
- Jilin University, China
- Peking University Health Science Center, China
- 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
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
- Christina L Stallings, Washington University School of Medicine, United States
Version history
- Received: August 20, 2021
- Preprint posted: September 6, 2021 (view preprint)
- Accepted: February 16, 2022
- Accepted Manuscript published: February 17, 2022 (version 1)
- 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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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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