{"doi":"10.1101/2021.09.06.459093","title":"<i>Legionella pneumophila</i> regulates host cell motility by targeting Phldb2 with a 14-3-3ζ-dependent protease effector","abstract":"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 identified the Dot/Icm effector Lem8 (Lpg1290) as a protease that interferes with host motility. We show that the protease activity of Lem8 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 PH domain-containing protein Phldb2 involved in cell migration as a target of Lem8 and demonstrate that Lem8 plays a role in the inhibition of host cell migration. Our results reveal a novel mechanism of inhibiting host cell motility by L. pneumophila for its virulence.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":226511,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9542,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":673937,"name":"Jingjing Luo","orcid":"0000-0002-4841-2624","position":1,"is_corresponding":false},{"id":308970,"name":"Dan Huang","orcid":"0000-0001-9079-0955","position":2,"is_corresponding":false},{"id":829556,"name":"Yunhao Tan","orcid":"0000-0002-5516-4980","position":3,"is_corresponding":false},{"id":729690,"name":"Yao Liu","orcid":"0000-0002-4330-2389","position":4,"is_corresponding":false},{"id":110342,"name":"Kaiwen Yu","orcid":"0000-0002-6050-8477","position":5,"is_corresponding":false},{"id":829557,"name":"Yong Zhang","orcid":"0000-0002-1303-0458","position":6,"is_corresponding":false},{"id":829558,"name":"Xiaoyun Liu","orcid":"0000-0001-7083-5263","position":7,"is_corresponding":false},{"id":829559,"name":"Dan Li","orcid":"0000-0002-3036-2374","position":8,"is_corresponding":false},{"id":395235,"name":"Zhao‐Qing Luo","orcid":"0000-0001-8890-6621","position":9,"is_corresponding":false},{"id":619301,"name":"Lei Song","orcid":"0000-0002-4115-065X","position":0,"is_corresponding":true}],"reference_count":87,"raw_metadata":null,"created_at":"2026-07-18T23:54:34.185847Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}