{"doi":"10.1016/j.jbc.2023.105378","title":"Progesterone receptor membrane component 1 facilitates Ca2+ signal amplification between endosomes and the endoplasmic reticulum","abstract":"Membrane contact sites (MCSs) between endosomes and the endoplasmic reticulum (ER) are thought to act as specialized trigger zones for Ca 2+ signaling, where local Ca 2+ released via endolysosomal ion channels is amplified by ER Ca 2+ -sensitive Ca 2+ channels into global Ca 2+ signals. Such amplification is integral to the action of the second messenger, nicotinic acid adenine dinucleotide phosphate (NAADP). However, functional regulators of inter-organellar Ca 2+ crosstalk between endosomes and the ER remain poorly defined. Here, we identify progesterone receptor membrane component 1 (PGRMC1), an ER transmembrane protein that undergoes a unique heme-dependent dimerization, as an interactor of the endosomal two pore channel, TPC1. NAADP-dependent Ca 2+ signals were potentiated by PGRMC1 overexpression through enhanced functional coupling between endosomal and ER Ca 2+ stores and inhibited upon PGRMC1 knockdown. Point mutants in PGMRC1 or pharmacological manipulations that reduced its interaction with TPC1 were without effect. PGRMC1 therefore serves as a TPC1 interactor that regulates ER-endosomal coupling with functional implications for cellular Ca 2+ dynamics and potentially the distribution of heme.","journal":"Journal of Biological Chemistry","year":2023,"id":371762,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9628,"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":1047521,"name":"Sushil Kumar","orcid":"0000-0002-1364-314X","position":1,"is_corresponding":false},{"id":1132261,"name":"Yaping Lin-Moshier","orcid":null,"position":2,"is_corresponding":false},{"id":636723,"name":"James T. Slama","orcid":"0000-0001-6053-1522","position":3,"is_corresponding":false},{"id":528237,"name":"Eugen Brailoiu","orcid":null,"position":4,"is_corresponding":false},{"id":636722,"name":"Sandip Patel","orcid":"0000-0001-7247-2013","position":5,"is_corresponding":false},{"id":402891,"name":"Timothy F. Walseth","orcid":"0000-0003-2558-7859","position":6,"is_corresponding":false},{"id":606949,"name":"Jonathan S. Marchant","orcid":"0000-0001-6592-0877","position":7,"is_corresponding":false},{"id":606950,"name":"Gihan S. Gunaratne","orcid":"0000-0002-1094-5820","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-19T01:15:49.453761Z","pmid":"37866635","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":[]}