{"doi":"10.1101/2022.12.19.521097","title":"Calcium flux through ER-TGN contact sites facilitates cargo export","abstract":"Abstract Ca 2+ influx into the trans-Golgi Network (TGN) promotes secretory cargo sorting by the Ca 2+ -ATPase SPCA1 and the luminal Ca 2+ binding protein Cab45. Cab45 oligomerizes upon a local Ca 2+ influx, and Cab45 oligomers sequester and separate soluble secretory cargo from the bulk flow of proteins in the TGN. However, how this Ca 2+ flux into the lumen of the TGN is achieved remains elusive, as the cytosol has a very low steady-state Ca 2+ concentration. The TGN forms membrane contact sites (MCS) with the Endoplasmic Reticulum (ER), whereby the close apposition of the two organelles allows the protein-mediated exchange of molecular species such as lipids. Here we show that the TGN export of Cab45 clients requires the integrity of ER-TGN MCS and IP3R-dependent Ca 2+ fluxes in the MCS, suggesting Ca 2+ transfer between these organelles. Using an MCS-targeted Ca 2+ FRET sensor module, we measure the Ca 2+ flow in these sites in real-time. These data show for the first time that ER-TGN MCS facilitates Ca 2+ transfer required for SPCA1-dependent cargo sorting and export from the TGN, thus solving a fundamental question in cell biology. Summary The current study demonstrates that the trafficking of COMP and LyzC relies on Ca 2+ flux between the endoplasmic reticulum (ER) and trans-Golgi Network (TGN). This process requires the activity of IP3 receptors, present in ER membranes, and depends on the integrity of the membrane contact site between these two organelles.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":313743,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.954,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1012486,"name":"Rosaria Di Martino","orcid":"0000-0002-4877-3454","position":1,"is_corresponding":false},{"id":560954,"name":"Abhishek Kumar","orcid":"0000-0003-3235-1916","position":2,"is_corresponding":false},{"id":683720,"name":"Anup Parchure","orcid":"0000-0003-1452-799X","position":3,"is_corresponding":false},{"id":814087,"name":"Yeongho Kim","orcid":"0000-0002-1477-925X","position":4,"is_corresponding":false},{"id":1012487,"name":"Oliver Griesbeck","orcid":"0000-0001-5883-5594","position":5,"is_corresponding":false},{"id":270346,"name":"Martin A. Schwartz","orcid":"0000-0002-2071-1243","position":6,"is_corresponding":false},{"id":1012488,"name":"Alberto Luini","orcid":"0000-0002-8729-2549","position":7,"is_corresponding":false},{"id":336987,"name":"Julia von Blume","orcid":"0000-0001-6665-1592","position":8,"is_corresponding":false},{"id":336984,"name":"Bulat R. Ramazanov","orcid":"0000-0001-8335-3685","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-19T00:33:48.490749Z","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":[]}