TY - JOUR TI - Legionella pneumophila regulates host cell motility by targeting Phldb2 with a 14-3-3ζ-dependent protease effector AU - Song, Lei AU - Luo, Jingjing AU - Wang, Hongou AU - Huang, Dan AU - Tan, Yunhao AU - Liu, Yao AU - Wang, Yingwu AU - Yu, Kaiwen AU - Zhang, Yong AU - Liu, Xiaoyun AU - Li, Dan AU - Luo, Zhao-Qing A2 - Stallings, Christina L A2 - Van der Meer, Jos W VL - 11 PY - 2022 DA - 2022/02/17 SP - e73220 C1 - eLife 2022;11:e73220 DO - 10.7554/eLife.73220 UR - https://doi.org/10.7554/eLife.73220 AB - 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. KW - Legionella KW - macrophages KW - Dictyostelium JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -