{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T18:11:10Z","timestamp":1787508670756,"version":"build-2736575974"},"reference-count":70,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,11]],"date-time":"2023-01-11T00:00:00Z","timestamp":1673395200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB854-B08"],"award-info":[{"award-number":["SFB854-B08"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["ZS\/2016\/08\/80645"],"award-info":[{"award-number":["ZS\/2016\/08\/80645"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ABINEP","award":["SFB854-B08"],"award-info":[{"award-number":["SFB854-B08"]}]},{"name":"ABINEP","award":["ZS\/2016\/08\/80645"],"award-info":[{"award-number":["ZS\/2016\/08\/80645"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2212CD8\u2212 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.<\/jats:p>","DOI":"10.3390\/ijms24021442","type":"journal-article","created":{"date-parts":[[2023,1,12]],"date-time":"2023-01-12T01:32:26Z","timestamp":1673487146000},"page":"1442","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Ca2+ Homeostasis by Plasma Membrane Ca2+ ATPase (PMCA) 1 Is Essential for the Development of DP Thymocytes"],"prefix":"10.3390","volume":"24","author":[{"given":"David","family":"Beckmann","sequence":"first","affiliation":[{"name":"Institute for Biochemistry and Cell Biology, Medical Faculty, Otto-von-Guericke-University Magdeburg, 39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Langnaese","sequence":"additional","affiliation":[{"name":"Institute for Biochemistry and Cell Biology, Medical Faculty, Otto-von-Guericke-University Magdeburg, 39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Gottfried","sequence":"additional","affiliation":[{"name":"Institute for Biochemistry and Cell Biology, Medical Faculty, Otto-von-Guericke-University Magdeburg, 39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Hradsky","sequence":"additional","affiliation":[{"name":"Institute for Biochemistry and Cell Biology, Medical Faculty, Otto-von-Guericke-University Magdeburg, 39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerry","family":"Tedford","sequence":"additional","affiliation":[{"name":"Institute for Biochemistry and Cell Biology, Medical Faculty, Otto-von-Guericke-University Magdeburg, 39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikhil","family":"Tiwari","sequence":"additional","affiliation":[{"name":"Department of Cellular Neuroscience, Leibniz Institute for Neurobiology, 39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Cellular Neuroscience, Leibniz Institute for Neurobiology, 39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus-Dieter","family":"Fischer","sequence":"additional","affiliation":[{"name":"Institute for Biochemistry and Cell Biology, Medical Faculty, Otto-von-Guericke-University Magdeburg, 39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Korthals","sequence":"additional","affiliation":[{"name":"Institute for Biochemistry and Cell Biology, Medical Faculty, Otto-von-Guericke-University Magdeburg, 39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/nri3667","article-title":"Positive and negative selection of the T cell repertoire: What thymocytes see (and don\u2019t see)","volume":"14","author":"Klein","year":"2014","journal-title":"Nat. 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