{"doi":"10.1085/jgp.202213324","title":"Piezo2 interacts with E-cadherin in specialized gastrointestinal epithelial mechanoreceptors","abstract":"Piezo2 is a mechanically gated ion channel most commonly expressed by specialized mechanoreceptors, such as the enteroendocrine cells (EECs) of the gastrointestinal epithelium. A subpopulation of EECs expresses Piezo2 and functionally resembles the skin's touch sensors, called Merkel cells. Low-magnitude mechanical stimuli delivered to the mucosal layer are primarily sensed by mechanosensitive EECs in a process we term \"gut touch.\" Piezo2 transduces cellular forces into ionic currents, a process that is sensitive to bilayer tension and cytoskeletal depolymerization. E-cadherin is a widely expressed protein that mediates cell-cell adhesion in epithelia and interacts with scaffold proteins that anchor it to actin fibers. E-cadherin was shown to interact with Piezo2 in immortalized cell models. We hypothesized that the Piezo2-E-cadherin interaction is important for EEC mechanosensitivity. To test this, we used super-resolution imaging, co-immunoprecipitation, and functional assays in primary tissues from mice and gut organoids. In tissue EECs and intestinal organoids, we observed multiple Piezo2 cellular pools, including one that overlaps with actin and E-cadherin at the cells' lateral walls. Further, E-cadherin co-immunoprecipitated with Piezo2 in the primary colonic epithelium. We found that E-cadherin knockdown decreases mechanosensitive calcium responses in mechanically stimulated primary EECs. In all, our results demonstrate that Piezo2 localizes to the lateral wall of EECs, where it physically interacts with E-cadherin and actin. They suggest that the Piezo2-E-cadherin-actin interaction is important for mechanosensitivity in the gut epithelium and possibly in tissues where E-cadherin and Piezo2 are co-expressed in epithelial mechanoreceptors, such as skin, lung, and bladder.","journal":"The Journal of General Physiology","year":2024,"id":443589,"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":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9583,"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":1258204,"name":"Jeric P. Hernandez","orcid":"0000-0002-8170-0783","position":1,"is_corresponding":false},{"id":732547,"name":"Yaroslav Fedyshyn","orcid":"0000-0002-2456-2062","position":2,"is_corresponding":false},{"id":413652,"name":"Anthony J. Treichel","orcid":"0000-0002-4393-7034","position":3,"is_corresponding":false},{"id":469451,"name":"Vikram Joshi","orcid":"0000-0002-4625-9427","position":4,"is_corresponding":false},{"id":1258205,"name":"Kimberlee Kossick","orcid":"0000-0001-8120-7617","position":5,"is_corresponding":false},{"id":1258206,"name":"Kalpana R. Betageri","orcid":"0000-0003-1320-8313","position":6,"is_corresponding":false},{"id":305799,"name":"Gianrico Farrugia","orcid":"0000-0003-3473-5235","position":7,"is_corresponding":false},{"id":504895,"name":"Brooke R. Druliner","orcid":"0000-0001-9254-8097","position":8,"is_corresponding":false},{"id":370718,"name":"Arthur Beyder","orcid":"0000-0002-9225-4854","position":9,"is_corresponding":false},{"id":643026,"name":"Arnaldo Mercado‐Perez","orcid":"0000-0001-8036-6771","position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":null,"created_at":"2026-07-19T02:01:29.001453Z","pmid":"39495178","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":[]}