{"doi":"10.1101/2025.05.13.653717","title":"Phactr4 influences macrophage lamellipodial structure and dynamics through Arp2/3 complex and Ezrin regulation","abstract":"Dynamic cycles of actin remodeling drive membrane protrusion and retraction events essential for macrophage function. Phosphoregulation of actin-associated proteins plays a key role, but the factors that determine the spatiotemporal balance between kinases and phosphatases is less well understood in this context. Here, we identify the Protein Phosphatase 1 (PP1)-binding protein Phactr4 as a critical regulator of cytoskeletal remodeling. Phactr4 loss disrupts lamellipodial architecture, which results in uncoordinated migration and disrupted iC3b-mediated phagocytosis. Unstable membrane dynamics underlie the Phactr4 knockdown phenotypes. Phactr4 is recruited to the leading edge via interaction with active Arp2/3 complex, and strongly correlates with membrane retraction. Phactr4 loss leads to ezrin hyperphosphorylation, and membrane protrusion defects in these cells are reversed by ezrin inhibition. Our findings position Phactr4 as a critical PP1-dependent coordinator of cytoskeletal remodeling during macrophage migration and phagocytosis. Recent reports have linked Phactr4 to several human disease states, which may be due to its influence on actin dynamics.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":565909,"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":0.9585,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":485001,"name":"Jeremy D. Rotty","orcid":"0000-0002-7782-9672","position":1,"is_corresponding":false},{"id":869545,"name":"Rohini Manickam","orcid":null,"position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-19T02:56:32.546082Z","pmid":"40462895","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":[]}