{"doi":"10.1371/journal.pone.0123018","title":"Filamin-A Increases the Stability and Plasma Membrane Expression of Polycystin-2","abstract":null,"journal":"PLOS ONE","year":2015,"id":664483,"datarank":0.8143652155140797,"base_score":2.8903717578961645,"endowment":2.8903717578961645,"self_citation_contribution":0.4335557636844247,"citation_network_contribution":0.380809451829655,"self_endowment_contribution":0.4335557636844247,"citer_contribution":0.380809451829655,"corpus_percentile":null,"corpus_rank":null,"citation_count":17,"citer_count":17,"citers_with_citation_signal":15,"citers_with_endowment":15,"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":461660,"name":"Wang Zheng","orcid":"0000-0002-7050-6133","position":1,"is_corresponding":false},{"id":1735048,"name":"Zuocheng Wang","orcid":null,"position":2,"is_corresponding":false},{"id":1735049,"name":"JungWoo Yang","orcid":null,"position":3,"is_corresponding":false},{"id":308159,"name":"Shaimaa Hussein","orcid":"0000-0003-0849-9670","position":4,"is_corresponding":false},{"id":1735050,"name":"Jingfeng Tang","orcid":null,"position":5,"is_corresponding":false},{"id":1735051,"name":"Xing-Zhen Chen","orcid":null,"position":6,"is_corresponding":false},{"id":389129,"name":"Qian Wang","orcid":"0000-0002-5031-0686","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Filamin-A Increases the Stability and Plasma Membrane Expression of Polycystin-2","abstract":"Polycystin-2 (PC2), encoded by the PKD2 gene, is mutated in ~15% of autosomal dominant polycystic kidney disease. Filamins are actin-binding proteins implicated in scaffolding and membrane stabilization. Here we studied the effects of filamin on PC2 stability using filamin-deficient human melanoma M2, filamin-A (FLNA)-replete A7, HEK293 and IMCD cells together with FLNA siRNA/shRNA knockdown (KD). We found that the presence of FLNA is associated with higher total and plasma membrane PC2 protein expression. Western blotting analysis in combination with FLNA KD showed that FLNA in A7 cells represses PC2 degradation, prolonging the half-life from 2.3 to 4.4 hours. By co-immunoprecipitation and Far Western blotting we found that the FLNA C-terminus (FLNAC) reduces the FLNA-PC2 binding and PC2 expression, presumably through competing with FLNA for binding PC2. We further found that FLNA mediates PC2 binding with actin through forming complex PC2-FLNA-actin. FLNAC acted as a blocking peptide and disrupted the link of PC2 with actin through disrupting the PC2-FLNA-actin complex. Finally, we demonstrated that the physical interaction of PC2-FLNA is Ca-dependent. Taken together, our current study indicates that FLNA anchors PC2 to the actin cytoskeleton through complex PC2-FLNA-actin to reduce degradation and increase stability, and possibly regulate PC2 function in a Ca-dependent manner.","is_dataset_classified":null,"base_score":2.8903717578961645,"endowment":2.8903717578961645,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"25861040","pmcid":"PMC4393133","openalex_id":"https://openalex.org/W1980974986","authors":[],"funders":[{"funder_name":"Canadian Institutes of Health Research","grant_id":"MOP 89977","title":null},{"funder_name":"Natural Sciences and Engineering Research Council of Canada","grant_id":"unidentified","title":"unidentified"}],"total_grants":2,"fwci":1.1245,"citation_percentile":0.80246699,"influential_citations":0,"citation_trend":[{"year":2016,"count":2},{"year":2017,"count":2},{"year":2018,"count":1},{"year":2020,"count":6},{"year":2021,"count":4},{"year":2022,"count":1},{"year":2025,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0123018&type=printable","host_type":"journal"},{"url":"https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0123018&type=printable","host_type":"publisher"},{"url":"http://dx.plos.org/10.1371/journal.pone.0123018","host_type":"publisher"},{"url":"https://doi.org/10.1371/journal.pone.0123018","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/25861040","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4393133","host_type":"repository"},{"url":"https://doaj.org/article/48d88576d5ae497fa7823e063ca1fde6","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC4393133","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC4393133?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1371/journal.pone.0123018","host_type":""},{"url":"https://dx.doi.org/10.1371/journal.pone.0123018","host_type":""}],"fields_of_study":["Genetic and Kidney Cyst Diseases","Fetal and Pediatric Neurological Disorders","Renal and related cancers","0301 basic medicine","0303 health sciences","03 medical and health sciences"],"mesh_terms":["Animals","Calcium","Cell Line","Cell Membrane","Humans","Actin Cytoskeleton","Recombinant Fusion Proteins","Multiprotein Complexes","Green Fluorescent Proteins","TRPP Cation Channels","Mice","Protein Interaction Domains and Motifs","Protein Stability","Gene Knockdown Techniques","HEK293 Cells","Proteolysis","Filamins"],"keywords":["FLNA","Filamin","Cell biology","Actin","Actin cytoskeleton","Immunoprecipitation","Biology","Blot","Cytoskeleton","Chemistry","Genetics","Gene","Cell","TRPP Cation Channels","Protein Stability","Science","Filamins","Recombinant Fusion Proteins","Q","Cell Membrane","Green Fluorescent Proteins","R","Cell Line","Mice","HEK293 Cells","Gene Knockdown Techniques","Multiprotein Complexes","Proteolysis","Medicine","Animals","Humans","Calcium","Protein Interaction Domains and Motifs","Research Article"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-13T03:05:43.362333Z","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":[]}