{"doi":"10.1242/jcs.206789","title":"Phosphorylation hotspot in the C-terminal domain of occludin regulates the dynamics of epithelial junctional complexes","abstract":"<jats:title>ABSTRACT</jats:title>\n               <jats:p>The apical junctional complex (AJC), which includes tight junctions (TJs) and adherens junctions (AJs), determines the epithelial polarity, cell-cell adhesion and permeability barrier. An intriguing characteristic of a TJ is the dynamic nature of its multiprotein complex. Occludin is the most mobile TJ protein, but its significance in TJ dynamics is poorly understood. On the basis of phosphorylation sites, we distinguished a sequence in the C-terminal domain of occludin as a regulatory motif (ORM). Deletion of ORM and expression of a deletion mutant of occludin in renal and intestinal epithelia reduced the mobility of occludin at the TJs. ORM deletion attenuated Ca2+ depletion, osmotic stress and hydrogen peroxide-induced disruption of TJs, AJs and the cytoskeleton. The double point mutations T403A/T404A, but not T403D/T404D, in occludin mimicked the effects of ORM deletion on occludin mobility and AJC disruption by Ca2+ depletion. Both Y398A/Y402A and Y398D/Y402D double point mutations partially blocked AJC disruption. Expression of a deletion mutant of occludin attenuated collective cell migration in the renal and intestinal epithelia. Overall, this study reveals the role of ORM and its phosphorylation in occludin mobility, AJC dynamics and epithelial cell migration.</jats:p>","journal":"Journal of Cell Science","year":2018,"id":593114,"datarank":0.9562417462166803,"base_score":3.1354942159291497,"endowment":3.1354942159291497,"self_citation_contribution":0.47032413238937254,"citation_network_contribution":0.48591761382730786,"self_endowment_contribution":0.47032413238937254,"citer_contribution":0.48591761382730786,"corpus_percentile":null,"corpus_rank":null,"citation_count":22,"citer_count":20,"citers_with_citation_signal":16,"citers_with_endowment":16,"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":732169,"name":"Hina Mir","orcid":"0000-0003-1973-199X","position":1,"is_corresponding":false},{"id":673630,"name":"Ruchika Gangwar","orcid":"0000-0002-2907-0411","position":2,"is_corresponding":false},{"id":337430,"name":"Avtar S. Meena","orcid":"0000-0003-2213-2488","position":3,"is_corresponding":false},{"id":1137315,"name":"Shrunali Amin","orcid":"0009-0009-5032-2212","position":4,"is_corresponding":false},{"id":492177,"name":"Pradeep K. Shukla","orcid":"0000-0003-2515-9766","position":5,"is_corresponding":false},{"id":655509,"name":"Kesha Dalal","orcid":"0000-0002-1107-975X","position":6,"is_corresponding":false},{"id":1517980,"name":"Takuya Suzuki","orcid":"0000-0003-2502-6496","position":7,"is_corresponding":false},{"id":492178,"name":"Radhakrishna Rao","orcid":"0000-0002-5906-8371","position":8,"is_corresponding":false},{"id":1517979,"name":"Bhargavi Manda","orcid":"0000-0001-5618-3967","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Phosphorylation hotspot in the C-terminal domain of occludin regulates the dynamics of epithelial junctional complexes","abstract":"<jats:title>ABSTRACT</jats:title>\n               <jats:p>The apical junctional complex (AJC), which includes tight junctions (TJs) and adherens junctions (AJs), determines the epithelial polarity, cell-cell adhesion and permeability barrier. An intriguing characteristic of a TJ is the dynamic nature of its multiprotein complex. Occludin is the most mobile TJ protein, but its significance in TJ dynamics is poorly understood. On the basis of phosphorylation sites, we distinguished a sequence in the C-terminal domain of occludin as a regulatory motif (ORM). Deletion of ORM and expression of a deletion mutant of occludin in renal and intestinal epithelia reduced the mobility of occludin at the TJs. ORM deletion attenuated Ca2+ depletion, osmotic stress and hydrogen peroxide-induced disruption of TJs, AJs and the cytoskeleton. The double point mutations T403A/T404A, but not T403D/T404D, in occludin mimicked the effects of ORM deletion on occludin mobility and AJC disruption by Ca2+ depletion. Both Y398A/Y402A and Y398D/Y402D double point mutations partially blocked AJC disruption. Expression of a deletion mutant of occludin attenuated collective cell migration in the renal and intestinal epithelia. Overall, this study reveals the role of ORM and its phosphorylation in occludin mobility, AJC dynamics and epithelial cell migration.</jats:p>","is_dataset_classified":null,"base_score":3.1354942159291497,"endowment":3.1354942159291497,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"29507118","pmcid":"PMC5963837","openalex_id":"https://openalex.org/W2789342649","authors":[],"funders":[{"funder_name":"University of Tennessee Health Science Center","grant_id":"AA12307","title":null},{"funder_name":"National Institutes of Health","grant_id":"DK55532","title":null},{"funder_name":"NIAAA NIH HHS","grant_id":"R01 AA012307","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R56 DK055532","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK055532","title":null}],"total_grants":5,"fwci":1.0839,"citation_percentile":0.77202143,"influential_citations":0,"citation_trend":[{"year":2018,"count":2},{"year":2019,"count":4},{"year":2020,"count":3},{"year":2021,"count":1},{"year":2022,"count":4},{"year":2023,"count":2},{"year":2024,"count":1},{"year":2025,"count":3},{"year":2026,"count":2}],"oa_status":"bronze","license":"http://www.biologists.com/user-licence-1-1/","oa_locations":[{"url":"https://jcs.biologists.org/content/joces/131/7/jcs206789.full.pdf","host_type":"journal"},{"url":"https://jcs.biologists.org/content/joces/131/7/jcs206789.full.pdf","host_type":"publisher"},{"url":"https://syndication.highwire.org/content/doi/10.1242/jcs.206789","host_type":"publisher"},{"url":"https://journals.biologists.com/jcs/article-pdf/doi/10.1242/jcs.206789/3505319/jcs206789.pdf","host_type":"publisher"},{"url":"http://journals.biologists.com/jcs/article-pdf/doi/10.1242/jcs.206789/2058378/jcs_206789v1.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1242/jcs.206789","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/29507118","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5963837","host_type":"repository"},{"url":"http://jcs.biologists.org/cgi/content/short/131/7/jcs206789","host_type":"repository"}],"fields_of_study":["Barrier Structure and Function Studies","Cancer-related molecular mechanisms research","Connexins and lens biology","Adherens Junctions","Animals","Calcium","Cell Movement","Cell Polarity","Cytoskeleton","Dogs","Epithelial Cells","Fluorescence Recovery After Photobleaching","Green Fluorescent Proteins","Humans","Intercellular Junctions","Madin Darby Canine Kidney Cells","Occludin","Phosphoproteins","Phosphorylation","Point Mutation","Protein Domains","Tight Junctions"],"mesh_terms":["Protein Domains","Animals","Calcium","Cell Movement","Cytoskeleton","Dogs","Epithelial Cells","Humans","Intercellular Junctions","Phosphoproteins","Phosphorylation","Cell Polarity","Point Mutation","Tight Junctions","Adherens Junctions","Fluorescence Recovery After Photobleaching","Green Fluorescent Proteins","Madin Darby Canine Kidney Cells","Occludin"],"keywords":["Occludin","Adherens junction","Tight junction","Biology","Cell biology","Phosphorylation","Cell junction","Cell polarity","Claudin","Cadherin","Cell","Biochemistry","Cytoskeleton","cell migration"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-26T17:17:02.496947Z","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":[]}