{"doi":"10.17615/zcwn-1p53","title":"Preferential Assembly of Epithelial Sodium Channel (ENaC) Subunits in Xenopus Oocytes: ROLE OF FURIN-MEDIATED ENDOGENOUS PROTEOLYSIS","abstract":"The epithelial sodium channel (ENaC) is preferentially assembled into heteromeric αβγ complexes. The α and γ (not β) subunits undergo proteolytic cleavage by endogenous furin-like activity correlating with increased ENaC function. We identified full-length subunits and their fragments at the cell surface, as well as in the intracellular pool, for all homo- and heteromeric combinations (α, β, γ, αβ, αγ, βγ, and αβγ). We assayed corresponding channel function as amiloride-sensitive sodium transport (INa). We varied furin-mediated proteolysis by mutating the P1 site in α and/or γ subunit furin consensus cleavage sites (αmut and γmut). Our findings were as follows. (i) The β subunit alone is not transported to the cell surface nor cleaved upon assembly with the α and/or γ subunits. (ii) The α subunit alone (or in combination with β and/or γ) is efficiently transported to the cell surface; a surface-expressed 65-kDa α ENaC fragment is undetected in αmutβγ, and INa is decreased by 60%. (iii) The γ subunit alone does not appear at the cell surface; γ co-expressed with α reaches the surface but is not detectably cleaved; and γ in αβγ complexes appears mainly as a 76-kDa species in the surface pool. Although basal INa of αβγmut was similar to αβγ, γmut was not detectably cleaved at the cell surface. Thus, furin-mediated cleavage is not essential for participation of α and γ in αβγ heteromers. Basal INa is reduced by preventing furin-mediated cleavage of the α, but not γ, subunits. Residual current in the absence of furin-mediated proteolysis may be due to non-furin endogenous proteases.","journal":"UNC Libraries","year":2020,"id":112183,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9583,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":531528,"name":"M. Jackson Stutts","orcid":"0000-0002-3159-7802","position":1,"is_corresponding":false},{"id":468241,"name":"Bernard C. Rossier","orcid":"0000-0003-2415-1180","position":2,"is_corresponding":false},{"id":531529,"name":"Dmitri Firsov","orcid":"0000-0002-3168-1238","position":3,"is_corresponding":false},{"id":532530,"name":"Agustı́n Garcı́a-Caballero","orcid":null,"position":4,"is_corresponding":false},{"id":531527,"name":"M. P. Harris","orcid":"0000-0002-9559-5830","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:13:13.874980Z","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":[]}