{"doi":"10.1083/jcb.139.7.1719","title":"Cytoskeletal Protein ABP-280 Directs the Intracellular Trafficking of Furin and Modulates Proprotein Processing in the Endocytic Pathway","abstract":"<jats:p>Furin catalyzes the proteolytic maturation of many proproteins within the trans-Golgi network (TGN)/endosomal system. Furin's cytosolic domain (cd) directs both the compartmentalization to and transit between its manifold processing compartments (i.e., TGN/biosynthetic pathway, cell surface, and endosomes). Here we report the identification of the first furin cd sorting protein, ABP-280 (nonmuscle filamin), an actin gelation protein. The furin cd was used as bait in a yeast two-hybrid screen to identify ABP-280 as a furin-binding protein. Binding analyses in vitro and coimmunoprecipitation studies in vivo showed that furin and ABP-280 interact directly and that ABP-280 tethers furin molecules to the cell surface. Quantitative analysis of both ABP-280-deficient and genetically replete cells showed that ABP-280 modulates the rate of internalization of furin but not of the transferrin receptor, a cycling receptor. However, although ABP-280 directs the rate of furin internalization, the efficiency of sorting of the endoprotease from the cell surface to early endosomes is independent of expression of ABP-280. By contrast, efficient sorting of furin from early endosomes to the TGN requires expression of ABP-280. In addition, ABP-280 is also required for the correct localization of late endosomes (dextran bead uptake) and lysosomes (LAMP-1 staining), demonstrating a pleiotropic role for this actin binding protein in the organization of cellular compartments and directing protein traffic. Finally, and consistent with the trafficking studies on furin, we showed that ABP-280 modulates the processing of furin substrates in the endocytic but not the biosynthetic pathways. The novel roles of ABP-280 and the cytoskeleton in the sorting of furin in the TGN/ endosomal system and the formation of proprotein processing compartments are discussed.</jats:p>","journal":"The Journal of Cell Biology","year":1997,"id":613638,"datarank":0.7433740586401892,"base_score":4.955827057601261,"endowment":4.955827057601261,"self_citation_contribution":0.7433740586401892,"citation_network_contribution":0.0,"self_endowment_contribution":0.7433740586401892,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":141,"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":704086,"name":"Laurel Thomas","orcid":null,"position":1,"is_corresponding":false},{"id":1580987,"name":"Robin A. 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Furin's cytosolic domain (cd) directs both the compartmentalization to and transit between its manifold processing compartments (i.e., TGN/biosynthetic pathway, cell surface, and endosomes). Here we report the identification of the first furin cd sorting protein, ABP-280 (nonmuscle filamin), an actin gelation protein. The furin cd was used as bait in a yeast two-hybrid screen to identify ABP-280 as a furin-binding protein. Binding analyses in vitro and coimmunoprecipitation studies in vivo showed that furin and ABP-280 interact directly and that ABP-280 tethers furin molecules to the cell surface. Quantitative analysis of both ABP-280-deficient and genetically replete cells showed that ABP-280 modulates the rate of internalization of furin but not of the transferrin receptor, a cycling receptor. However, although ABP-280 directs the rate of furin internalization, the efficiency of sorting of the endoprotease from the cell surface to early endosomes is independent of expression of ABP-280. By contrast, efficient sorting of furin from early endosomes to the TGN requires expression of ABP-280. In addition, ABP-280 is also required for the correct localization of late endosomes (dextran bead uptake) and lysosomes (LAMP-1 staining), demonstrating a pleiotropic role for this actin binding protein in the organization of cellular compartments and directing protein traffic. Finally, and consistent with the trafficking studies on furin, we showed that ABP-280 modulates the processing of furin substrates in the endocytic but not the biosynthetic pathways. The novel roles of ABP-280 and the cytoskeleton in the sorting of furin in the TGN/ endosomal system and the formation of proprotein processing compartments are discussed.</jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"9412467","pmcid":"PMC1424222","openalex_id":null,"authors":[],"funders":[{"funder_name":"NIDDK NIH HHS","grant_id":"T32 DK007674","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"DK-44629","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"DK-37274","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"DK-40608","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"F32 DK009394","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"T32 DK007680","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK037274","title":null},{"funder_name":"National Institutes of Health","grant_id":"5R01DK040608-10","title":"STRUCTURE AND FUNCTION OF THE TRANSFERRIN RECEPTOR"},{"funder_name":"National Institutes of Health","grant_id":"2R01DK044629-05A1","title":"HUMAN FURIN PROCESSING ENDOPROTEASE"},{"funder_name":"National Institutes of Health","grant_id":"5R01DK037274-16","title":"REGULATION OF PROTEIN TRAFFIC IN NEUROENDOCRINE CELLS"}],"total_grants":10,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"bronze","license":null,"oa_locations":[{"url":"http://jcb.rupress.org/content/139/7/1719.full.pdf","host_type":"publisher"},{"url":"https://rupress.org/jcb/article-pdf/139/7/1719/1488899/29208.pdf","host_type":"publisher"},{"url":"https://europepmc.org/articles/PMC1424222","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC1424222?pdf=render","host_type":"Europe_PMC"},{"url":"https://doi.org/10.1083/jcb.139.7.1719","host_type":""},{"url":"https://pubmed.ncbi.nlm.nih.gov/9412467","host_type":""},{"url":"https://dx.doi.org/10.1083/jcb.139.7.1719","host_type":""}],"fields_of_study":["0301 basic medicine","0303 health sciences","03 medical and health sciences"],"mesh_terms":["Cell Line","Tumor Cells, Cultured","Cell Membrane","Endosomes","Lysosomes","Animals","Humans","Microfilament Proteins","Furin","Subtilisins","Carrier Proteins","Receptors, Transferrin","Contractile Proteins","Protein Precursors","Cell Compartmentation","Endocytosis","Protein Processing, Post-Translational","Amino Acid Sequence","Base Sequence","Models, Biological","Molecular Sequence Data","Filamins","Chlorocebus aethiops"],"keywords":["Furin","Base Sequence","Filamins","Cell Membrane","Microfilament Proteins","Molecular Sequence Data","Endosomes","Models, Biological","Endocytosis","Cell Compartmentation","Cell Line","Contractile Proteins","Chlorocebus aethiops","Animals","Humans","Amino Acid Sequence","Protein Precursors","Carrier Proteins","Lysosomes","Protein Processing, Post-Translational"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"gen"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-02T08:48:01.800170Z","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":[]}