{"doi":"10.1083/jcb.202410094","title":"Direct measurements of luminal Ca2+ with endo-lysosomal GFP-aequorin reveal functional IP3 receptors","abstract":"Endo-lysosomes are considered acidic Ca2+ stores, but direct measurements of luminal Ca2+ within them are limited. Here, we report that the Ca2+-sensitive luminescent protein aequorin does not reconstitute with its cofactor at highly acidic pH but that a significant fraction of the probe is functional within a mildly acidic compartment when targeted to the endo-lysosomal system. We leveraged this probe (ELGA) to report Ca2+ dynamics in this compartment. We show that Ca2+ uptake is ATP-dependent and sensitive to blockers of ER Ca2+ pumps. We find that the Ca2+ mobilizing messenger IP3 evokes robust luminal responses in wild-type cells, but not in IP3R knockout cells. Responses were comparable to those evoked by activation of the endo-lysosomal ion channels TPCs and TRPMLs. Stimulation with IP3-forming agonists also mobilized the store in intact cells. Super-resolution microscopy analysis was consistent with the presence of IP3Rs within the endo-lysosomal system. Our data reveal a physiologically relevant, IP3-sensitive store of Ca2+ within the endo-lysosomal system.","journal":"The Journal of Cell Biology","year":2025,"id":538358,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9597,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1424976,"name":"Patricia Torres-vidal","orcid":"0009-0005-9616-8258","position":1,"is_corresponding":false},{"id":1424977,"name":"Alba Delrio-Lorenzo","orcid":"0000-0002-3176-3380","position":2,"is_corresponding":false},{"id":1424978,"name":"Carla Rodríguez-Crespo","orcid":"0009-0000-1174-6658","position":3,"is_corresponding":false},{"id":1424979,"name":"Francisco J. Aulestia","orcid":"0000-0002-7841-812X","position":4,"is_corresponding":false},{"id":1424980,"name":"Jonathan Rojo-Ruiz","orcid":"0000-0003-1155-2858","position":5,"is_corresponding":false},{"id":1424981,"name":"Beatriz Callejo","orcid":"0009-0003-4592-0994","position":6,"is_corresponding":false},{"id":643194,"name":"Bridget M. McVeigh","orcid":"0000-0003-4200-6016","position":7,"is_corresponding":false},{"id":876037,"name":"Marco Keller","orcid":"0000-0003-4792-3980","position":8,"is_corresponding":false},{"id":653213,"name":"Christian Grimm","orcid":"0000-0002-0177-5559","position":9,"is_corresponding":false},{"id":885785,"name":"Viola Oorschot","orcid":"0000-0002-8122-8271","position":10,"is_corresponding":false},{"id":301040,"name":"Vera Y. Moiseenkova‐Bell","orcid":"0000-0002-0589-4053","position":11,"is_corresponding":false},{"id":147718,"name":"David I Yule","orcid":"0000-0002-6743-0668","position":12,"is_corresponding":false},{"id":1424982,"name":"Javier Garcı́a-Sancho","orcid":"0000-0003-4573-7930","position":13,"is_corresponding":false},{"id":636722,"name":"Sandip Patel","orcid":"0000-0001-7247-2013","position":14,"is_corresponding":false},{"id":649329,"name":"Marı́a Teresa Alonso","orcid":"0000-0002-9176-3788","position":15,"is_corresponding":false},{"id":1424975,"name":"Belén Calvo","orcid":"0000-0003-1415-1363","position":0,"is_corresponding":true}],"reference_count":74,"raw_metadata":null,"created_at":"2026-07-19T02:52:21.389196Z","pmid":"41201441","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":[]}