{"doi":"10.1242/jcs.259075","title":"A general role for TANGO1, encoded by <i>MIA3</i>, in secretory pathway organization and function","abstract":"<jats:title>ABSTRACT</jats:title>\n               <jats:p>Complex machinery is required to drive secretory cargo export from the endoplasmic reticulum (ER), which is an essential process in eukaryotic cells. In vertebrates, the MIA3 gene encodes two major forms of transport and Golgi organization protein 1 (TANGO1S and TANGO1L), which have previously been implicated in selective trafficking of procollagen. Using genome engineering of human cells, light microscopy, secretion assays, genomics and proteomics, we show that disruption of the longer form, TANGO1L, results in relatively minor defects in secretory pathway organization and function, including having limited impacts on procollagen secretion. In contrast, loss of both long and short forms results in major defects in cell organization and secretion. These include a failure to maintain the localization of ERGIC53 (also known as LMAN1) and SURF4 to the ER–Golgi intermediate compartment and dramatic changes to the ultrastructure of the ER–Golgi interface. Disruption of TANGO1 causes significant changes in early secretory pathway gene and protein expression, and impairs secretion not only of large proteins, but of all types of secretory cargo, including small soluble proteins. Our data support a general role for MIA3/TANGO1 in maintaining secretory pathway structure and function in vertebrate cells.</jats:p>","journal":"Journal of Cell Science","year":2021,"id":653713,"datarank":1.18972986455127,"base_score":3.828641396489095,"endowment":3.828641396489095,"self_citation_contribution":0.5742962094733643,"citation_network_contribution":0.6154336550779055,"self_endowment_contribution":0.5742962094733643,"citer_contribution":0.6154336550779055,"corpus_percentile":null,"corpus_rank":null,"citation_count":45,"citer_count":40,"citers_with_citation_signal":28,"citers_with_endowment":28,"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":823552,"name":"Nicola L. Stevenson","orcid":"0000-0001-8967-7277","position":1,"is_corresponding":false},{"id":1705719,"name":"Judith M. Mantell","orcid":"0000-0002-9061-8933","position":2,"is_corresponding":false},{"id":1705720,"name":"Chris R. Neal","orcid":"0000-0001-6604-280X","position":3,"is_corresponding":false},{"id":1705721,"name":"Alex Paterson","orcid":"0000-0003-3025-8347","position":4,"is_corresponding":false},{"id":483205,"name":"Kate J. Heesom","orcid":"0000-0002-5418-5392","position":5,"is_corresponding":false},{"id":174054,"name":"David Stephens","orcid":"0000-0001-5297-3240","position":6,"is_corresponding":false},{"id":1705718,"name":"Janine McCaughey","orcid":"0000-0001-7709-2597","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"A general role for TANGO1, encoded by <i>MIA3</i>, in secretory pathway organization and function","abstract":"<jats:title>ABSTRACT</jats:title>\n               <jats:p>Complex machinery is required to drive secretory cargo export from the endoplasmic reticulum (ER), which is an essential process in eukaryotic cells. In vertebrates, the MIA3 gene encodes two major forms of transport and Golgi organization protein 1 (TANGO1S and TANGO1L), which have previously been implicated in selective trafficking of procollagen. Using genome engineering of human cells, light microscopy, secretion assays, genomics and proteomics, we show that disruption of the longer form, TANGO1L, results in relatively minor defects in secretory pathway organization and function, including having limited impacts on procollagen secretion. In contrast, loss of both long and short forms results in major defects in cell organization and secretion. These include a failure to maintain the localization of ERGIC53 (also known as LMAN1) and SURF4 to the ER–Golgi intermediate compartment and dramatic changes to the ultrastructure of the ER–Golgi interface. Disruption of TANGO1 causes significant changes in early secretory pathway gene and protein expression, and impairs secretion not only of large proteins, but of all types of secretory cargo, including small soluble proteins. Our data support a general role for MIA3/TANGO1 in maintaining secretory pathway structure and function in vertebrate cells.</jats:p>","is_dataset_classified":null,"base_score":3.8066624897703196,"endowment":3.8066624897703196,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"34350936","pmcid":"PMC8524724","openalex_id":"https://openalex.org/W3191834672","authors":[],"funders":[{"funder_name":"Medical Research Council","grant_id":"MR/P000177/1","title":"High-resolution imaging and time-resolved proteomic profiling of COPII-dependent procollagen packaging."},{"funder_name":"Biotechnology and Biological Sciences Research Council","grant_id":"BB/T001984/1 BB/L014181/1 BB/L01386X/1","title":null},{"funder_name":"Engineering and Physical Sciences Research Council","grant_id":"BB/L01386X/1","title":"BrisSynBio: Bristol Centre for Synthetic Biology"},{"funder_name":"Biotechnology and Biological Sciences Research Council","grant_id":"BB/L014181/1","title":"Photo-oxidation and cryofluorescence for Correlative Light Electron Microscopy."},{"funder_name":"Biotechnology and Biological Sciences Research Council","grant_id":"BB/T001984/1","title":"Opportunities to modulate extracellular matrix secretion and assembly for long term health"},{"funder_name":"University of Bristol","grant_id":"","title":null}],"total_grants":6,"fwci":2.6803,"citation_percentile":0.9063333,"influential_citations":0,"citation_trend":[{"year":2021,"count":1},{"year":2022,"count":6},{"year":2023,"count":7},{"year":2024,"count":13},{"year":2025,"count":11},{"year":2026,"count":6}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"https://journals.biologists.com/jcs/article-pdf/134/17/jcs259075/2103872/jcs259075.pdf","host_type":"journal"},{"url":"https://journals.biologists.com/jcs/article-pdf/134/17/jcs259075/2103872/jcs259075.pdf","host_type":"publisher"},{"url":"http://journals.biologists.com/jcs/article-pdf/doi/10.1242/jcs.259075/2092824/jcs259075.pdf","host_type":"publisher"},{"url":"https://journals.biologists.com/jcs/article-pdf/doi/10.1242/jcs.259075/3488625/jcs259075.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1242/jcs.259075","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/34350936","host_type":"repository"},{"url":"https://research-information.bris.ac.uk/en/publications/6fe3648f-b60e-4ec2-9625-f1d38568392d","host_type":"repository"},{"url":"http://europepmc.org/pmc/articles/PMC8524724","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/8524724","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC8524724","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1242/jcs.259075","host_type":""},{"url":"https://dx.doi.org/10.1242/jcs.259075","host_type":""},{"url":"https://hdl.handle.net/1983/6fe3648f-b60e-4ec2-9625-f1d38568392d","host_type":""},{"url":"https://research-information.bris.ac.uk/ws/files/299022488/Full_text_PDF_final_published_version_.pdf","host_type":""},{"url":"https://doi.org/https://doi.org/10.1242/jcs.259075","host_type":""}],"fields_of_study":["Cellular transport and secretion","Endoplasmic Reticulum Stress and Disease","Genetic and Kidney Cyst Diseases","0301 basic medicine","0303 health sciences","03 medical and health sciences","Animals","Aryl Hydrocarbon Receptor Nuclear Translocator","COP-Coated Vesicles","Endoplasmic Reticulum","Golgi Apparatus","Humans","Membrane Proteins","Protein Transport","Secretory Pathway"],"mesh_terms":["Animals","Endoplasmic Reticulum","Golgi Apparatus","Humans","Membrane Proteins","Protein Transport","COP-Coated Vesicles","Aryl Hydrocarbon Receptor Nuclear Translocator","Secretory Pathway"],"keywords":["Biology","Golgi apparatus","Secretion","Endoplasmic reticulum","Secretory pathway","Cell biology","Secretory protein","Function (biology)","Proteomics","Transport protein","Gene","Genetics","Biochemistry","Collagen","Golgi","Copii","Ergic","Tango1","Aryl Hydrocarbon Receptor Nuclear Translocator","610","Membrane Proteins","Protein Transport","Animals","Humans","synthetic biology","/dk/atira/pure/core/keywords/biodesign_SRI; 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