{"doi":"10.1091/mbc.e04-07-0555","title":"Actin-depolymerizing Factor and Cofilin-1 Play Overlapping Roles in Promoting Rapid F-Actin Depolymerization in Mammalian Nonmuscle Cells","abstract":"<jats:p>Actin-depolymerizing factor (ADF)/cofilins are small actin-binding proteins found in all eukaryotes. In vitro, ADF/cofilins promote actin dynamics by depolymerizing and severing actin filaments. However, whether ADF/cofilins contribute to actin dynamics in cells by disassembling “old” actin filaments or by promoting actin filament assembly through their severing activity is a matter of controversy. Analysis of mammalian ADF/cofilins is further complicated by the presence of multiple isoforms, which may contribute to actin dynamics by different mechanisms. We show that two isoforms, ADF and cofilin-1, are expressed in mouse NIH 3T3, B16F1, and Neuro 2A cells. Depleting cofilin-1 and/or ADF by siRNA leads to an accumulation of F-actin and to an increase in cell size. Cofilin-1 and ADF seem to play overlapping roles in cells, because the knockdown phenotype of either protein could be rescued by overexpression of the other one. Cofilin-1 and ADF knockdown cells also had defects in cell motility and cytokinesis, and these defects were most pronounced when both ADF and cofilin-1 were depleted. Fluorescence recovery after photobleaching analysis and studies with an actin monomer-sequestering drug, latrunculin-A, demonstrated that these phenotypes arose from diminished actin filament depolymerization rates. These data suggest that mammalian ADF and cofilin-1 promote cytoskeletal dynamics by depolymerizing actin filaments and that this activity is critical for several processes such as cytokinesis and cell motility.</jats:p>","journal":"Molecular Biology of the Cell","year":2005,"id":685425,"datarank":0.8925963828881591,"base_score":5.950642552587727,"endowment":5.950642552587727,"self_citation_contribution":0.8925963828881591,"citation_network_contribution":0.0,"self_endowment_contribution":0.8925963828881591,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":383,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1790722,"name":"Eija Paunola","orcid":null,"position":1,"is_corresponding":false},{"id":319784,"name":"Maria K. Vartiainen","orcid":"0000-0002-2017-0475","position":2,"is_corresponding":false},{"id":460720,"name":"Pekka Lappalainen","orcid":"0000-0001-6227-0354","position":3,"is_corresponding":false},{"id":1595862,"name":"Pirta Hotulainen","orcid":"0000-0003-0764-8582","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Actin-depolymerizing Factor and Cofilin-1 Play Overlapping Roles in Promoting Rapid F-Actin Depolymerization in Mammalian Nonmuscle Cells","abstract":"<jats:p>Actin-depolymerizing factor (ADF)/cofilins are small actin-binding proteins found in all eukaryotes. In vitro, ADF/cofilins promote actin dynamics by depolymerizing and severing actin filaments. However, whether ADF/cofilins contribute to actin dynamics in cells by disassembling “old” actin filaments or by promoting actin filament assembly through their severing activity is a matter of controversy. Analysis of mammalian ADF/cofilins is further complicated by the presence of multiple isoforms, which may contribute to actin dynamics by different mechanisms. We show that two isoforms, ADF and cofilin-1, are expressed in mouse NIH 3T3, B16F1, and Neuro 2A cells. Depleting cofilin-1 and/or ADF by siRNA leads to an accumulation of F-actin and to an increase in cell size. Cofilin-1 and ADF seem to play overlapping roles in cells, because the knockdown phenotype of either protein could be rescued by overexpression of the other one. Cofilin-1 and ADF knockdown cells also had defects in cell motility and cytokinesis, and these defects were most pronounced when both ADF and cofilin-1 were depleted. Fluorescence recovery after photobleaching analysis and studies with an actin monomer-sequestering drug, latrunculin-A, demonstrated that these phenotypes arose from diminished actin filament depolymerization rates. These data suggest that mammalian ADF and cofilin-1 promote cytoskeletal dynamics by depolymerizing actin filaments and that this activity is critical for several processes such as cytokinesis and cell motility.</jats:p>","is_dataset_classified":null,"base_score":5.950642552587727,"endowment":5.950642552587727,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"15548599","pmcid":"PMC545901","openalex_id":"https://openalex.org/W1994844322","authors":[],"funders":[],"total_grants":0,"fwci":4.7659,"citation_percentile":0.95696536,"influential_citations":0,"citation_trend":[{"year":2012,"count":32},{"year":2013,"count":22},{"year":2014,"count":19},{"year":2015,"count":22},{"year":2016,"count":20},{"year":2017,"count":16},{"year":2018,"count":18},{"year":2019,"count":7},{"year":2020,"count":13},{"year":2021,"count":17},{"year":2022,"count":11},{"year":2023,"count":15},{"year":2024,"count":10},{"year":2025,"count":12},{"year":2026,"count":1}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/545901","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/545901","host_type":"repository"},{"url":"https://doi.org/10.1091/mbc.e04-07-0555","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/15548599","host_type":"repository"},{"url":"http://europepmc.org/pmc/articles/PMC545901","host_type":"repository"}],"fields_of_study":["Cellular Mechanics and Interactions","Cell Adhesion Molecules Research","Silk-based biomaterials and applications","Actins","Animals","Blotting, Western","Bridged Bicyclo Compounds, Heterocyclic","Cell Line, Tumor","Cell Movement","Cell Size","Cofilin 1","Cytokinesis","Destrin","Fibroblasts","Fibronectins","Fluorescein-5-isothiocyanate","Fluorescence Recovery After Photobleaching","Fluorescent Antibody Technique","Fluorescent Dyes","Gene Silencing","Indoles","Kinetics","Melanoma, Experimental","Mice","Microfilament Proteins","Microscopy, Video","NIH 3T3 Cells","Protein Isoforms","RNA, Small Interfering","Stress Fibers","Thiazoles","Thiazolidines"],"mesh_terms":["Actins","Animals","Cell Movement","Fibroblasts","Fibronectins","Fluorescent Antibody Technique","Fluorescent Dyes","Indoles","Kinetics","Melanoma, Experimental","Microfilament Proteins","Thiazoles","Blotting, Western","Fluorescein-5-isothiocyanate","Microscopy, Video","Bridged Bicyclo Compounds, Heterocyclic","Protein Isoforms","Gene Silencing","Stress Fibers","RNA, Small Interfering","Fluorescence Recovery After Photobleaching","NIH 3T3 Cells","Cell Line, Tumor","Cell Size","Cytokinesis","Cofilin 1","Destrin","Mice","Thiazolidines"],"keywords":["Cofilin","Biology","Cell biology","Actin","Depolymerization","Actin remodeling","Actina","Actin remodeling of neurons","Actin-binding protein","MDia1","Cytoskeleton","Actin cytoskeleton","Genetics","Cell","Materials science"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-18T16:39:15.312431Z","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":[]}