| Autor: |
Beckmann D; Institute for Biochemistry and Cell Biology, Medical Faculty, Otto-von-Guericke-University Magdeburg, 39120 Magdeburg, Germany., Langnaese K; Institute for Biochemistry and Cell Biology, Medical Faculty, Otto-von-Guericke-University Magdeburg, 39120 Magdeburg, Germany., Gottfried A; Institute for Biochemistry and Cell Biology, Medical Faculty, Otto-von-Guericke-University Magdeburg, 39120 Magdeburg, Germany., Hradsky J; Institute for Biochemistry and Cell Biology, Medical Faculty, Otto-von-Guericke-University Magdeburg, 39120 Magdeburg, Germany., Tedford K; Institute for Biochemistry and Cell Biology, Medical Faculty, Otto-von-Guericke-University Magdeburg, 39120 Magdeburg, Germany., Tiwari N; Department of Cellular Neuroscience, Leibniz Institute for Neurobiology, 39120 Magdeburg, Germany., Thomas U; Department of Cellular Neuroscience, Leibniz Institute for Neurobiology, 39120 Magdeburg, Germany., Fischer KD; Institute for Biochemistry and Cell Biology, Medical Faculty, Otto-von-Guericke-University Magdeburg, 39120 Magdeburg, Germany., Korthals M; Institute for Biochemistry and Cell Biology, Medical Faculty, Otto-von-Guericke-University Magdeburg, 39120 Magdeburg, Germany. |
| Abstrakt: |
The strength of Ca 2+ signaling is a hallmark of T cell activation, yet the role of Ca 2+ 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 Ca 2+ 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 Ca 2+ 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 Ca 2+ homeostasis throughout this process. PMCA1 is, therefore, non-redundant in keeping cellular Ca 2+ levels low in the early thymocyte development required for the DN to DP transition. |
