{"doi":"10.1073/pnas.2104090118","title":"Inside-out regulation of E-cadherin conformation and adhesion","abstract":"Cadherin cell-cell adhesion proteins play key roles in tissue morphogenesis and wound healing. Cadherin ectodomains bind in two conformations, X-dimers and strand-swap dimers, with different adhesive properties. However, the mechanisms by which cells regulate ectodomain conformation are unknown. Cadherin intracellular regions associate with several actin-binding proteins including vinculin, which are believed to tune cell-cell adhesion by remodeling the actin cytoskeleton. Here, we show at the single-molecule level, that vinculin association with the cadherin cytoplasmic region allosterically converts weak X-dimers into strong strand-swap dimers and that this process is mediated by myosin II-dependent changes in cytoskeletal tension. We also show that in epithelial cells, ∼70% of apical cadherins exist as strand-swap dimers while the remaining form X-dimers, providing two cadherin pools with different adhesive properties. Our results demonstrate the inside-out regulation of cadherin conformation and establish a mechanistic role for vinculin in this process.","journal":"Proceedings of the National Academy of Sciences","year":2021,"id":163148,"datarank":0.5676284450877392,"base_score":3.784189633918261,"endowment":3.784189633918261,"self_citation_contribution":0.5676284450877392,"citation_network_contribution":0.0,"self_endowment_contribution":0.5676284450877392,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":43,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.95,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":561161,"name":"Andrew Vae Priest","orcid":null,"position":1,"is_corresponding":false},{"id":560329,"name":"Chi‐Fu Yen","orcid":"0000-0001-5498-2773","position":2,"is_corresponding":false},{"id":560330,"name":"Joleen S. Cheah","orcid":"0000-0002-1848-9583","position":3,"is_corresponding":false},{"id":334690,"name":"Willem‐Jan Pannekoek","orcid":"0000-0001-6394-5384","position":4,"is_corresponding":false},{"id":560331,"name":"Martijn Gloerich","orcid":"0000-0002-0034-4642","position":5,"is_corresponding":false},{"id":560332,"name":"Soichiro Yamada","orcid":"0000-0001-6413-0814","position":6,"is_corresponding":false},{"id":355155,"name":"Sanjeevi Sivasankar","orcid":"0000-0003-2593-0477","position":7,"is_corresponding":false},{"id":560328,"name":"Ramesh Koirala","orcid":"0000-0003-0101-3420","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:45:17.971865Z","pmid":"34301871","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":[]}