{"doi":"10.1128/mcb.00336-08","title":"The Transforming Rho Family GTPase Wrch-1 Disrupts Epithelial Cell Tight Junctions and Epithelial Morphogenesis","abstract":null,"journal":"Molecular and Cellular Biology","year":2009,"id":593556,"datarank":0.6038027536102726,"base_score":4.02535169073515,"endowment":4.02535169073515,"self_citation_contribution":0.6038027536102726,"citation_network_contribution":0.0,"self_endowment_contribution":0.6038027536102726,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":55,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1040185,"name":"Jamie K. Alan","orcid":"0009-0006-4878-1688","position":1,"is_corresponding":false},{"id":477452,"name":"James P. Madigan","orcid":"0000-0002-0503-3704","position":2,"is_corresponding":false},{"id":204563,"name":"Alan S. Fanning","orcid":null,"position":3,"is_corresponding":false},{"id":449324,"name":"Adrienne D. Cox","orcid":"0000-0002-4901-2454","position":4,"is_corresponding":false},{"id":255608,"name":"Donita C. Brady","orcid":"0000-0002-2786-2802","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"The Transforming Rho Family GTPase Wrch-1 Disrupts Epithelial Cell Tight Junctions and Epithelial Morphogenesis","abstract":"Wrch-1, an atypical and transforming Rho GTPase, regulates cellular activities including proliferation and actin organization, but its functions and effectors remain poorly characterized. We show here that Wrch-1 distributes along the apical and basolateral membranes in MDCK cells and binds the cell polarity protein Par6 in a GTP-dependent manner. Activated Wrch-1 negatively regulates the kinetics of tight junction (TJ) assembly during epithelial cell polarization but has no detectable effect on overall cell polarity in confluent monolayers. It also causes a dramatic cytoskeletal reorganization and multilayering in cells grown in two-dimensional culture and disrupts cystogenesis of cells grown in three-dimensional (3D) culture. Similarly, short hairpin RNA-mediated knockdown of Wrch-1 perturbs cystogenesis in 3D culture, suggesting that tight regulation of Wrch-1 activity is necessary for normal epithelial morphogenesis. A weakly transforming effector domain mutant of activated Wrch-1 that inhibits Par6 binding abrogates the ability of Wrch-1 to disrupt TJ formation, actin organization, and epithelial morphogenesis. We hypothesize that Wrch-1-induced morphological and growth transformation may occur in part through Par6-mediated disruption of TJs and actin organization.","is_dataset_classified":null,"base_score":4.02535169073515,"endowment":4.02535169073515,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19064640","pmcid":"PMC2643799","openalex_id":"https://openalex.org/W2032370959","authors":[],"funders":[{"funder_name":"NIDDK NIH HHS","grant_id":"DK61397","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"T32-GM007040","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"T32 GM007040","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"T32 GM008581","title":null},{"funder_name":"NCI NIH HHS","grant_id":"CA109550","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R01 CA109550","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R56 DK061397","title":null},{"funder_name":"NCI NIH HHS","grant_id":"T32-CA071341","title":null},{"funder_name":"NCI NIH HHS","grant_id":"T32 CA071341","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"T32-GM008581","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK061397","title":null}],"total_grants":11,"fwci":2.0083,"citation_percentile":0.84758247,"influential_citations":0,"citation_trend":[{"year":2012,"count":3},{"year":2013,"count":2},{"year":2014,"count":4},{"year":2015,"count":3},{"year":2016,"count":2},{"year":2017,"count":1},{"year":2018,"count":4},{"year":2019,"count":4},{"year":2020,"count":4},{"year":2022,"count":2},{"year":2023,"count":4},{"year":2024,"count":4},{"year":2025,"count":2},{"year":2026,"count":1}],"oa_status":"bronze","license":"https://journals.asm.org/non-commercial-tdm-license","oa_locations":[{"url":"https://mcb.asm.org/content/mcb/29/4/1035.full.pdf","host_type":"journal"},{"url":"https://mcb.asm.org/content/mcb/29/4/1035.full.pdf","host_type":"publisher"},{"url":"https://journals.asm.org/doi/pdf/10.1128/MCB.00336-08","host_type":"publisher"},{"url":"https://www.tandfonline.com/doi/pdf/10.1128/MCB.00336-08","host_type":"publisher"},{"url":"https://doi.org/10.1128/mcb.00336-08","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/19064640","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2643799","host_type":"repository"}],"fields_of_study":["Hippo pathway signaling and YAP/TAZ","Wnt/β-catenin signaling in development and cancer","Hedgehog Signaling Pathway Studies"],"mesh_terms":["Actins","Animals","Cell Adhesion","Chlorocebus aethiops","Dogs","Enzyme Activation","Epithelial Cells","Epithelium","Guanosine Triphosphate","Humans","Morphogenesis","Mutation","Protein Binding","Cell Polarity","Protein Structure, Tertiary","Tight Junctions","COS Cells","rho GTP-Binding Proteins","Protein Transport","Cell Shape","Adaptor Proteins, Signal Transducing","Cell Proliferation"],"keywords":["Cell biology","Cell polarity","Biology","Morphogenesis","Actin","Rac GTP-Binding Proteins","Tight junction","Cytoskeleton","GTPase","Epithelial polarity","CDC42","Actin cytoskeleton","Effector","RAC1","Cell","Signal transduction","Biochemistry","Gene"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Clean water and sanitation"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-27T11:26:57.323331Z","pmid":null,"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":[]}