{"doi":"10.1126/sciadv.adm8663","title":"SLC26A4-AP-2 mu2 interaction regulates SLC26A4 plasma membrane abundance in the endolymphatic sac","abstract":"Decreased presence or activity of human SLC26A4 at the plasma membrane is a common cause of hearing loss. SLC26A4 (Pendrin) is necessary for normal reabsorption of endolymph, the fluid bathing the inner ear. We identified the μ2 subunit of adaptor protein 2 (AP-2) complex required for clathrin-mediated endocytosis as a protein-partner of SLC26A4 involved in regulating its plasma membrane abundance. We showed that, in the endolymphatic sac, where fluid reabsorption occurs, SLC26A4 is localized along the apical microvilli of mitochondria-rich cells, in contact with the endolymph, and associated with clathrin-coated pits where μ2 and AP-2 are present. Based on SLC26A4 structure, the elements involved in SLC26A4-μ2 interaction were identified and validated experimentally, allowing modeling of this interaction at the atomic level. Pharmacological inhibition of clathrin-mediated endocytosis led to an increased plasma membrane abundance of hemagglutinin-tagged SLC26A4 virally or endogenously expressed in mitochondria-rich cells. These results indicate that the SLC26A4-μ2 interaction regulates SLC26A4 abundance at the apical surface of mitochondria-rich cells.","journal":"Science Advances","year":2024,"id":469459,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9592,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":370772,"name":"Cristina Fenollar‐Ferrer","orcid":"0000-0003-4953-8891","position":1,"is_corresponding":false},{"id":717549,"name":"Kevin Isgrig","orcid":null,"position":2,"is_corresponding":false},{"id":1303552,"name":"Ya-Xian Wang","orcid":null,"position":3,"is_corresponding":false},{"id":1303553,"name":"Kerstin Valente","orcid":null,"position":4,"is_corresponding":false},{"id":1303143,"name":"Juleh Eide","orcid":"0009-0002-8551-2787","position":5,"is_corresponding":false},{"id":778208,"name":"Keiji Honda","orcid":"0000-0002-3411-8539","position":6,"is_corresponding":false},{"id":471477,"name":"Wade W. Chien","orcid":"0000-0002-3865-3918","position":7,"is_corresponding":false},{"id":277236,"name":"Ronald S. Petralia","orcid":"0000-0003-4423-8355","position":8,"is_corresponding":false},{"id":286497,"name":"Lijin Dong","orcid":"0000-0001-7401-9511","position":9,"is_corresponding":false},{"id":70685,"name":"Thomas B. Friedman","orcid":"0000-0003-4614-6630","position":10,"is_corresponding":false},{"id":62801,"name":"Juan S. Bonifacino","orcid":"0000-0002-5673-6370","position":11,"is_corresponding":false},{"id":331646,"name":"Andrew J. Griffith","orcid":"0000-0002-5684-3109","position":12,"is_corresponding":false},{"id":331644,"name":"Isabelle Roux","orcid":"0000-0001-7527-7520","position":13,"is_corresponding":false},{"id":1106958,"name":"Hyun Jae Lee","orcid":"0000-0001-6568-5053","position":0,"is_corresponding":true}],"reference_count":76,"raw_metadata":null,"created_at":"2026-07-19T02:05:32.241298Z","pmid":"39383236","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":[]}