{"doi":"10.1016/j.bbamcr.2025.119990","title":"Paraoxonase 3 regulates the pore-forming α subunit of the large-conductance K+ channel","abstract":"Paraoxonase 3 (PON3) is expressed in the aldosterone-sensitive distal nephron (ASDN) where the fine tuning of Na + and K + homeostasis in the kidney occurs. Flow-induced K + secretion within intercalated cells (ICs) of the ASDN is mediated by the large-conductance K + (BK) channels. We have previously shown that renal PON3 expression was altered by dietary K + intake and that Pon3 knockout (KO) mice had lower plasma [K + ]. These findings led us to hypothesize that PON3 may have a role in regulating renal K + secretion by altering BK channel functional expression. The present study shows that both PON3 and the pore-forming α subunit of the BK channel (αBK) are expressed in ICs of mouse kidney and that the two proteins co-localize to the same cellular compartments when expressed in HEK293 cells. Using a biochemical approach, we show that PON3 interacts with αBK endogenously in the mouse kidney and when both proteins were co-expressed in HEK293 cells. We also examined the effects of PON3 on αBK expression and channel activity in HEK293 cells. We found that paxilline-sensitive BK currents were significantly reduced by PON3 expression, likely a consequence of lower surface abundance of αBK. Consistent with this finding, we observed a stronger αBK staining signal in ICs of Pon3 KO kidneys. Together, our data suggest that PON3 negatively regulates the functional expression of BK channels.","journal":"Biochimica et Biophysica Acta (BBA) - Molecular Cell Research","year":2025,"id":565727,"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":0.9667,"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":520970,"name":"Andrew J. Nickerson","orcid":"0000-0001-7604-2344","position":1,"is_corresponding":false},{"id":425931,"name":"Nicolás Montalbetti","orcid":"0000-0003-2897-9540","position":2,"is_corresponding":false},{"id":356415,"name":"Stephanie M. Mutchler","orcid":"0000-0002-4288-4452","position":3,"is_corresponding":false},{"id":425933,"name":"Marcelo D. Carattino","orcid":"0000-0003-1901-1618","position":4,"is_corresponding":false},{"id":356418,"name":"Thomas R. Kleyman","orcid":"0000-0002-2413-5415","position":5,"is_corresponding":false},{"id":425930,"name":"Shujie Shi","orcid":"0000-0003-3785-853X","position":6,"is_corresponding":false},{"id":1075607,"name":"Sarah Christine Whelan","orcid":"0000-0001-8790-4886","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-19T02:56:32.546082Z","pmid":"40368269","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":[]}