{"doi":"10.1016/j.jbc.2024.107432","title":"Modulation of TMEM16B channel activity by the calcium-activated chloride channel regulator 4 (CLCA4) in human cells","abstract":"The Ca 2+ -activated Cl − channel regulator CLCA1 potentiates the activity of the Ca 2+ -activated Cl − channel (CaCC) TMEM16A by directly engaging the channel at the cell surface, inhibiting its reinternalization and increasing Ca 2+ -dependent Cl − current (I CaCC ) density. We now present evidence of functional pairing between two other CLCA and TMEM16 protein family members, namely CLCA4 and the CaCC TMEM16B. Similar to CLCA1, (i) CLCA4 is a self-cleaving metalloprotease, and the N-terminal portion (N-CLCA4) is secreted; (ii) the von Willebrand factor type A (VWA) domain in N-CLCA4 is sufficient to potentiate I CaCC in HEK293T cells; and (iii) this is mediated by the metal ion-dependent adhesion site motif within VWA. The results indicate that, despite the conserved regulatory mechanism and homology between CLCA1 and CLCA4, CLCA4-dependent I CaCC are carried by TMEM16B, rather than TMEM16A. Our findings show specificity in CLCA/TMEM16 interactions and suggest broad physiological and pathophysiological links between these two protein families.","journal":"Journal of Biological Chemistry","year":2024,"id":465635,"datarank":0.26876392038420827,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.0,"self_endowment_contribution":0.26876392038420827,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9601,"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":1297039,"name":"Zeynep Yurtsever","orcid":"0000-0001-6848-8602","position":1,"is_corresponding":false},{"id":374651,"name":"Kayla N. Berry","orcid":"0000-0002-1113-4798","position":2,"is_corresponding":false},{"id":302404,"name":"Conor McClenaghan","orcid":"0000-0002-0859-3854","position":3,"is_corresponding":false},{"id":1297513,"name":"Alyssa J Foy","orcid":null,"position":4,"is_corresponding":false},{"id":302405,"name":"Alex Hanson","orcid":"0000-0002-4931-0590","position":5,"is_corresponding":false},{"id":556821,"name":"Deborah F. Steinberg","orcid":null,"position":6,"is_corresponding":false},{"id":940590,"name":"Jessica A. Greven","orcid":null,"position":7,"is_corresponding":false},{"id":556246,"name":"Colin E. Kluender","orcid":"0000-0001-5238-4286","position":8,"is_corresponding":false},{"id":556248,"name":"Jennifer Alexander‐Brett","orcid":"0000-0002-2685-7139","position":9,"is_corresponding":false},{"id":302407,"name":"Colin G. Nichols","orcid":"0000-0002-4929-2134","position":10,"is_corresponding":false},{"id":374652,"name":"Tom J. Brett","orcid":"0000-0002-6871-6676","position":11,"is_corresponding":false},{"id":1297038,"name":"Monica Sala‐Rabanal","orcid":"0000-0001-8442-2099","position":0,"is_corresponding":true}],"reference_count":43,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:04:50.328230Z","pmid":"38825009","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":[]}