{"doi":"10.1083/jcb.202308124","title":"α-Catenin force-sensitive binding and sequestration of LZTS2 leads to cytokinesis failure","abstract":"Epithelial cells can become polyploid upon tissue injury, but mechanosensitive cues that trigger this state are poorly understood. Using an Madin Darby Canine Kidney (MDCK) cell knock-out/reconstitution system, we show that α-catenin mutants that alter force-sensitive binding to F-actin or middle (M)-domain promote cytokinesis failure and binucleation, particularly near epithelial wound-fronts. We identified Leucine Zipper Tumor Suppressor 2 (LZTS2), a factor previously implicated in abscission, as a conformation sensitive proximity partner of α-catenin. We show that LZTS2 enriches not only at midbody/intercellular bridges but also at apical adhering junctions. α-Catenin mutants with persistent M-domain opening show elevated junctional enrichment of LZTS2 compared with wild-type cells. LZTS2 knock-down leads to elevated rates of binucleation. These data implicate LZTS2 as a mechanosensitive effector of α-catenin that is critical for cytokinetic fidelity. This model rationalizes how persistent mechanoactivation of α-catenin may drive tension-induced polyploidization of epithelia after injury and suggests an underlying mechanism for how pathogenic α-catenin M-domain mutations drive macular dystrophy.","journal":"The Journal of Cell Biology","year":2024,"id":459079,"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":0.9594,"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":476409,"name":"Alex Yemelyanov","orcid":null,"position":1,"is_corresponding":false},{"id":1286329,"name":"Christopher Go","orcid":null,"position":2,"is_corresponding":false},{"id":698351,"name":"Sun K. Kim","orcid":"0000-0002-6033-6142","position":3,"is_corresponding":false},{"id":1045046,"name":"Jeanne M. Quinn","orcid":"0000-0002-7830-4659","position":4,"is_corresponding":false},{"id":878000,"name":"Annette S. Flozak","orcid":null,"position":5,"is_corresponding":false},{"id":36967,"name":"Phuong M. Le","orcid":"0000-0001-8639-1572","position":6,"is_corresponding":false},{"id":727943,"name":"Shannon Liang","orcid":null,"position":7,"is_corresponding":false},{"id":44860,"name":"Anne‐Claude Gingras","orcid":"0000-0002-6090-4437","position":8,"is_corresponding":false},{"id":680171,"name":"Mitsuhiko Ikura","orcid":"0000-0002-9524-1303","position":9,"is_corresponding":false},{"id":1074055,"name":"Noboru Ishiyama","orcid":"0000-0002-1426-6083","position":10,"is_corresponding":false},{"id":491981,"name":"Cara J. Gottardi","orcid":"0000-0003-0912-7617","position":11,"is_corresponding":false},{"id":1174656,"name":"Yuou Wang","orcid":"0000-0001-8675-8055","position":0,"is_corresponding":true}],"reference_count":97,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:03:55.280882Z","pmid":"39786338","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":[]}