{"doi":"10.3390/ijms24021442","title":"Ca2+ Homeostasis by Plasma Membrane Ca2+ ATPase (PMCA) 1 Is Essential for the Development of DP Thymocytes","abstract":"The strength of Ca2+ signaling is a hallmark of T cell activation, yet the role of Ca2+ homeostasis in developing T cells before expressing a mature T cell receptor is poorly understood. We aimed to unveil specific functions of the two plasma membrane Ca2+ ATPases expressed in T cells, PMCA1 and PMCA4. On a transcriptional and protein level we found that PMCA4 was expressed at low levels in CD4−CD8− double negative (DN) thymocytes and was even downregulated in subsequent stages while PMCA1 was present throughout development and upregulated in CD4+CD8+ double positive (DP) thymocytes. Mice with a targeted deletion of Pmca1 in DN3 thymocytes had an almost complete block of DP thymocyte development with an accumulation of DN4 thymocytes but severely reduced numbers of CD8+ immature single positive (ISP) thymocytes. The DN4 thymocytes of these mice showed strongly elevated basal cytosolic Ca2+ levels and a pre-mature CD5 expression, but in contrast to the DP thymocytes they were only mildly prone to apoptosis. Surprisingly, mice with a germline deletion of Pmca4 did not show any signs of altered progression through the developmental thymocyte stages, nor altered Ca2+ homeostasis throughout this process. PMCA1 is, therefore, non-redundant in keeping cellular Ca2+ levels low in the early thymocyte development required for the DN to DP transition.","journal":"International Journal of Molecular Sciences","year":2023,"id":368482,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9632,"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":1126826,"name":"Kristina Langnaese","orcid":null,"position":1,"is_corresponding":false},{"id":1126827,"name":"Anna Gottfried","orcid":null,"position":2,"is_corresponding":false},{"id":1126828,"name":"Johannes Hradsky","orcid":null,"position":3,"is_corresponding":false},{"id":1126446,"name":"Kerry Tedford","orcid":"0000-0002-0646-0214","position":4,"is_corresponding":false},{"id":1126447,"name":"Nikhil Tiwari","orcid":"0000-0003-1299-7226","position":5,"is_corresponding":false},{"id":764552,"name":"Ulrich Thomas","orcid":"0000-0002-4372-8611","position":6,"is_corresponding":false},{"id":948310,"name":"Klaus‐Dieter Fischer","orcid":"0000-0002-8996-4871","position":7,"is_corresponding":false},{"id":1126448,"name":"Mark Korthals","orcid":"0009-0007-5623-2280","position":8,"is_corresponding":false},{"id":1126825,"name":"David Beckmann","orcid":null,"position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":null,"created_at":"2026-07-19T01:15:20.453499Z","pmid":"36674959","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":[]}