{"doi":"10.17615/n796-qd81","title":"Loss of Arp2/3 induces an NF-κB–dependent, nonautonomous effect on chemotactic signaling","abstract":"A decrease in Arp2/3 levels results in an NF-κB–dependent increase in the expression of several secreted factors, resulting in nonautonomous effects on chemotaxis.Arp2/3-branched actin is critical for cytoskeletal dynamics and cell migration. However, perturbations and diseases affecting this network have phenotypes that cannot be fully explained by cell-autonomous effects. In this paper, we report nonautonomous effects of Arp2/3 depletion. We show that, upon Arp2/3 depletion, the expression of numerous genes encoding secreted factors, including chemokines, growth factors, and matrix metalloproteases, was increased, a signature resembling the senescence-associated secretory phenotype. These factors affected epidermal growth factor chemotaxis in a nonautonomous way, resolving the recent contradictions about the role of Arp2/3 in chemotaxis. We demonstrate that these genes were activated by nuclear factor κB via a CCM2–MEKK3 pathway that has been implicated in hyperosmotic stress signaling. Consistent with this, Arp2/3-depleted cells showed misregulation of volume control and reduced actin in the submembranous cortex. The defects in osmotic signaling in the Arp2/3-depleted cells can be rescued by hypoosmotic treatment. Thus, perturbations of Arp2/3 have nonautonomous effects that should be considered when evaluating experimental manipulations and diseases affecting the Arp2/3-actin cytoskeleton.","journal":"UNC Libraries","year":2020,"id":143277,"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":0.948,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":453521,"name":"James E. Bear","orcid":"0000-0002-8489-996X","position":1,"is_corresponding":false},{"id":2220,"name":"Gary L. Johnson","orcid":"0000-0003-2867-0551","position":2,"is_corresponding":false},{"id":11659,"name":"Jeremy M. Simon","orcid":"0000-0003-3906-1663","position":3,"is_corresponding":false},{"id":531398,"name":"Sreeja B. Asokan","orcid":null,"position":4,"is_corresponding":false},{"id":85400,"name":"Norman E. Sharpless","orcid":"0000-0001-7078-9455","position":5,"is_corresponding":false},{"id":610915,"name":"Congying Wu","orcid":"0000-0002-3223-7884","position":6,"is_corresponding":false},{"id":13386,"name":"Ian J. Davis","orcid":"0000-0002-1552-0960","position":7,"is_corresponding":false},{"id":544112,"name":"Albert S. Baldwin","orcid":"0000-0003-1246-1333","position":8,"is_corresponding":false},{"id":530857,"name":"Elizabeth M. Haynes","orcid":"0000-0002-5294-018X","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:17:38.432803Z","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":[]}