{"doi":"10.1016/j.celrep.2023.113628","title":"Two-pore channel-2 and inositol trisphosphate receptors coordinate Ca2+ signals between lysosomes and the endoplasmic reticulum","abstract":"Lysosomes and the endoplasmic reticulum (ER) are Ca 2+ stores mobilized by the second messengers NAADP and IP 3 , respectively. Here, we establish Ca 2+ signals between the two sources as fundamental building blocks that couple local release to global changes in Ca 2+ . Cell-wide Ca 2+ signals evoked by activation of endogenous NAADP-sensitive channels on lysosomes comprise both local and global components and exhibit a major dependence on ER Ca 2+ despite their lysosomal origin. Knockout of ER IP 3 receptor channels delays these signals, whereas expression of lysosomal TPC2 channels accelerates them. High-resolution Ca 2+ imaging reveals elementary events upon TPC2 opening and signals coupled to IP 3 receptors. Biasing TPC2 activation to a Ca 2+ -permeable state sensitizes local Ca 2+ signals to IP 3 . This increases the potency of a physiological agonist to evoke global Ca 2+ signals and activate a downstream target. Our data provide a conceptual framework to understand how Ca 2+ release from physically separated stores is coordinated.","journal":"Cell Reports","year":2023,"id":323196,"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":38,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9465,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":542325,"name":"Vikas Arige","orcid":"0000-0002-0589-1880","position":1,"is_corresponding":false},{"id":1037901,"name":"Ryo� Saito","orcid":"0000-0002-1927-8147","position":2,"is_corresponding":false},{"id":1038556,"name":"Qianru Mu","orcid":null,"position":3,"is_corresponding":false},{"id":527480,"name":"G. Cristina Brailoiu","orcid":"0000-0002-2512-6545","position":4,"is_corresponding":false},{"id":1037902,"name":"Gustavo J.S. Pereira","orcid":"0000-0002-6765-1276","position":5,"is_corresponding":false},{"id":876709,"name":"Stephen R. Bolsover","orcid":null,"position":6,"is_corresponding":false},{"id":876037,"name":"Marco Keller","orcid":"0000-0003-4792-3980","position":7,"is_corresponding":false},{"id":856019,"name":"Franz Bracher","orcid":"0000-0003-0009-8629","position":8,"is_corresponding":false},{"id":653213,"name":"Christian Grimm","orcid":"0000-0002-0177-5559","position":9,"is_corresponding":false},{"id":528237,"name":"Eugen Brailoiu","orcid":null,"position":10,"is_corresponding":false},{"id":606949,"name":"Jonathan S. Marchant","orcid":"0000-0001-6592-0877","position":11,"is_corresponding":false},{"id":147718,"name":"David I Yule","orcid":"0000-0002-6743-0668","position":12,"is_corresponding":false},{"id":636722,"name":"Sandip Patel","orcid":"0000-0001-7247-2013","position":13,"is_corresponding":false},{"id":876035,"name":"Yu Yuan","orcid":"0000-0002-4620-0249","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-19T01:07:52.377944Z","pmid":"38160394","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":[]}