{"doi":"10.3390/ijms23126745","title":"Kidney-Specific CAP1/Prss8-Deficient Mice Maintain ENaC-Mediated Sodium Balance through an Aldosterone Independent Pathway","abstract":"The serine protease prostasin (CAP1/Prss8, channel-activating protease-1) is a confirmed in vitro and in vivo activator of the epithelial sodium channel ENaC. To test whether proteolytic activity or CAP1/Prss8 abundance itself are required for ENaC activation in the kidney, we studied animals either hetero- or homozygous mutant at serine 238 (S238A; Prss8cat/+ and Prss8cat/cat), and renal tubule-specific CAP1/Prss8 knockout (Prss8PaxLC1) mice. When exposed to varying Na+-containing diets, no changes in Na+ and K+ handling and only minor changes in the expression of Na+ and K+ transporting protein were found in both models. Similarly, the α- or γENaC subunit cleavage pattern did not differ from control mice. On standard and low Na+ diet, Prss8cat/+ and Prss8cat/cat mice exhibited standard plasma aldosterone levels and unchanged amiloride-sensitive rectal potential difference indicating adapted ENaC activity. Upon Na+ deprivation, mice lacking the renal CAP1/Prss8 expression (Prss8PaxLC1) exhibit significantly decreased plasma aldosterone and lower K+ levels but compensate by showing significantly higher plasma renin activity. Our data clearly demonstrated that the catalytic activity of CAP1/Prss8 is dispensable for proteolytic ENaC activation. CAP1/Prss8-deficiency uncoupled ENaC activation from its aldosterone dependence, but Na+ homeostasis is maintained through alternative pathways.","journal":"International Journal of Molecular Sciences","year":2022,"id":280146,"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":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9641,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":954192,"name":"Yannick Jäger","orcid":"0000-0003-1712-3712","position":1,"is_corresponding":false},{"id":954604,"name":"Chloé Sergi","orcid":null,"position":2,"is_corresponding":false},{"id":954605,"name":"Anne‐Marie Mérillat","orcid":null,"position":3,"is_corresponding":false},{"id":954606,"name":"Thibaud Peyrollaz","orcid":null,"position":4,"is_corresponding":false},{"id":954193,"name":"Deepika Anand","orcid":"0000-0002-7844-7051","position":5,"is_corresponding":false},{"id":954194,"name":"Qing Wang","orcid":"0000-0001-6540-1858","position":6,"is_corresponding":false},{"id":954195,"name":"Frédérique Ino","orcid":"0009-0008-3077-9752","position":7,"is_corresponding":false},{"id":954196,"name":"Marc Maillard","orcid":"0000-0001-6428-0046","position":8,"is_corresponding":false},{"id":838065,"name":"Stephan Kellenberger","orcid":"0000-0003-1755-6198","position":9,"is_corresponding":false},{"id":954607,"name":"Ivan Gautschi","orcid":null,"position":10,"is_corresponding":false},{"id":376299,"name":"Roman Szabo","orcid":"0000-0002-7661-8718","position":11,"is_corresponding":false},{"id":371359,"name":"Thomas Bugge","orcid":"0000-0001-7046-4060","position":12,"is_corresponding":false},{"id":954197,"name":"Lotte K. Vogel","orcid":"0000-0001-9920-0982","position":13,"is_corresponding":false},{"id":609836,"name":"Edith Hümmler","orcid":"0000-0002-3887-2715","position":14,"is_corresponding":false},{"id":954608,"name":"Simona Frateschi","orcid":null,"position":15,"is_corresponding":false},{"id":954191,"name":"Elodie Ehret","orcid":"0000-0003-0181-4893","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-19T00:28:59.341002Z","pmid":"35743186","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":[]}