{"doi":"10.1242/jcs.153437","title":"Galectin-4-mediated transcytosis of transferrin receptor","abstract":"<jats:p>Some native epithelia, e.g. Retinal Pigment Epithelium (RPE) and Kidney Proximal Tubule (KPT) constitutively lack the basolateral sorting adaptor AP-1B; this results in many basolateral plasma membrane proteins repositioned to the apical domain, where they perform essential functions for their host organs. We recently reported the underlying apical polarity reversal mechanism: in the absence of AP-1B-mediated basolateral sorting, basolateral proteins are shuttled to the apical plasma membrane via a novel transcytotic pathway mediated by the plus-end kinesin KIF16B. Here, we demonstrate that this apical transcytotic pathway requires apical sorting of basolateral proteins mediated by apical signals and galectin-4. Using RPE and KPT cell lines, and AP-1B knocked-down MDCK cells, we show that mutation of the N-glycan linked to asparagine 727 in the basolateral marker Transferrin Receptor (TfR) or knock-down of galectin-4 inhibits TfR transcytosis to apical recycling endosomes and the apical plasma membrane and promotes TfR lysosomal targeting/degradation. Our results report a novel role of galectins in basolateral to apical epithelial transcytosis.</jats:p>","journal":"Journal of Cell Science","year":2014,"id":678500,"datarank":0.5416376868966337,"base_score":3.6109179126442243,"endowment":3.6109179126442243,"self_citation_contribution":0.5416376868966337,"citation_network_contribution":0.0,"self_endowment_contribution":0.5416376868966337,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":36,"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":237937,"name":"Ryan Schreiner","orcid":"0000-0002-7457-6606","position":1,"is_corresponding":false},{"id":281695,"name":"Ignacio Benedicto","orcid":"0000-0001-8081-1847","position":2,"is_corresponding":false},{"id":1772761,"name":"Enrique J. Rodriguez-Boulan","orcid":null,"position":3,"is_corresponding":false},{"id":1521013,"name":"Andres E. Perez Bay","orcid":"0000-0002-7830-1618","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Galectin-4-mediated transcytosis of transferrin receptor","abstract":"<jats:p>Some native epithelia, e.g. Retinal Pigment Epithelium (RPE) and Kidney Proximal Tubule (KPT) constitutively lack the basolateral sorting adaptor AP-1B; this results in many basolateral plasma membrane proteins repositioned to the apical domain, where they perform essential functions for their host organs. We recently reported the underlying apical polarity reversal mechanism: in the absence of AP-1B-mediated basolateral sorting, basolateral proteins are shuttled to the apical plasma membrane via a novel transcytotic pathway mediated by the plus-end kinesin KIF16B. Here, we demonstrate that this apical transcytotic pathway requires apical sorting of basolateral proteins mediated by apical signals and galectin-4. Using RPE and KPT cell lines, and AP-1B knocked-down MDCK cells, we show that mutation of the N-glycan linked to asparagine 727 in the basolateral marker Transferrin Receptor (TfR) or knock-down of galectin-4 inhibits TfR transcytosis to apical recycling endosomes and the apical plasma membrane and promotes TfR lysosomal targeting/degradation. Our results report a novel role of galectins in basolateral to apical epithelial transcytosis.</jats:p>","is_dataset_classified":null,"base_score":3.6109179126442243,"endowment":3.6109179126442243,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"25179596","pmcid":"PMC4197088","openalex_id":"https://openalex.org/W2024380105","authors":[],"funders":[{"funder_name":"NIGMS NIH HHS","grant_id":"GM34107","title":null},{"funder_name":"NEI NIH HHS","grant_id":"R01 EY008538","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"1K01DK102836-01","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"K01 DK102836","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM034107","title":null},{"funder_name":"NEI NIH HHS","grant_id":"EY08538","title":null}],"total_grants":6,"fwci":1.335,"citation_percentile":0.79347224,"influential_citations":0,"citation_trend":[{"year":2015,"count":4},{"year":2016,"count":5},{"year":2017,"count":2},{"year":2018,"count":4},{"year":2019,"count":4},{"year":2020,"count":6},{"year":2021,"count":1},{"year":2022,"count":4},{"year":2023,"count":3},{"year":2024,"count":2},{"year":2025,"count":1}],"oa_status":"closed","license":null,"oa_locations":[{"url":"http://journals.biologists.com/jcs/article-pdf/127/20/4457/1937015/jcs-127-20-4457.pdf","host_type":"publisher"},{"url":"http://journals.biologists.com/jcs/article-pdf/doi/10.1242/jcs.153437/2047107/jcs153437.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1242/jcs.153437","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/25179596","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4197088","host_type":"repository"},{"url":"http://jcs.biologists.org/cgi/content/short/127/20/4457","host_type":"repository"}],"fields_of_study":["Galectins and Cancer Biology","Cellular transport and secretion","Lysosomal Storage Disorders Research"],"mesh_terms":["Animals","Cell Line","Cell Membrane","Dogs","Epithelial Cells","Humans","Lysosomes","Mutation","Receptors, Transferrin","Endosomes","Cell Polarity","Protein Transport","Protein Sorting Signals","Adaptor Protein Complex 1","Adaptor Protein Complex beta Subunits","Galectin 4","Gene Knockdown Techniques","Transcytosis","Madin Darby Canine Kidney Cells"],"keywords":["Transcytosis","Cell biology","Apical membrane","Biology","Endosome","Epithelial polarity","Apical cell","Endocytosis","Cell polarity","Transferrin receptor","Transport protein","Transferrin","Epithelium","Receptor","Biochemistry","Cell","Intracellular","Galectin","Glycan","Rab11a"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-17T05:30:24.747575Z","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":[]}