{"doi":"10.1242/dmm.049762","title":"An interaction between OTULIN and SCRIB uncovers roles for linear ubiquitination in planar cell polarity","abstract":"Planar cell polarity (PCP) plays critical roles in developmental and homeostatic processes. Membrane presentation of PCP complexes containing Van Gogh-like (VANGL) transmembrane proteins is central to PCP and can be directed by the scaffold protein scribble (SCRIB). The role atypical linear ubiquitin (Met1-Ub) chains might play in PCP is unknown. Here, HEK293 cell-based interactomic analyses of the Met1-Ub deubiquitinase OTULIN revealed that OTULIN can interact with SCRIB. Moreover, Met1-Ub chains associated with VANGL2 and PRICKLE1, but not SCRIB, can direct VANGL2 surface presentation. Mouse embryos lacking Otulin showed variable neural tube malformations, including rare open neural tubes, a deficit associated with PCP disruption in mice. In Madin-Darby canine kidney cells, in which the enrichment of VANGL2-GFP proteins at cell-cell contacts represents activated PCP complexes, endogenous OTULIN was recruited to these sites. In the human MDA-MB-231 breast cancer cell model, OTULIN loss caused deficits in Wnt5a-induced filopodia extension and trafficking of transfected HA-VANGL2. Taken together, these findings support a role for linear (de)ubiquitination in PCP signaling. The association of Met1-Ub chains with PCP complex components offers new opportunities for integrating PCP signaling with OTULIN-dependent immune and inflammatory pathways.","journal":"Disease Models & Mechanisms","year":2023,"id":388671,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9507,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1158575,"name":"Sofiia Ivantsiv","orcid":null,"position":1,"is_corresponding":false},{"id":1158576,"name":"Rieko Niibori","orcid":null,"position":2,"is_corresponding":false},{"id":366991,"name":"Wade H. Dunham","orcid":"0000-0003-4748-4842","position":3,"is_corresponding":false},{"id":1137834,"name":"Brooke A. Green","orcid":null,"position":4,"is_corresponding":false},{"id":1158178,"name":"Liang Zhao","orcid":"0000-0001-8841-351X","position":5,"is_corresponding":false},{"id":44860,"name":"Anne‐Claude Gingras","orcid":"0000-0002-6090-4437","position":6,"is_corresponding":false},{"id":1158179,"name":"Sabine P. Cordes","orcid":"0000-0002-3133-3655","position":7,"is_corresponding":false},{"id":1158177,"name":"Stephanie M. Almeida","orcid":"0000-0003-1129-4588","position":0,"is_corresponding":true}],"reference_count":113,"raw_metadata":null,"created_at":"2026-07-19T01:18:18.214733Z","pmid":"37589075","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":[]}