A complex of Neuroplastin and Plasma Membrane Ca2+ ATPase controls T cell activation
| Autor: | Rodrigo Herrera-Molina, Klaus-Dieter Fischer, Juliane Handschuh, Werner Zuschratter, Michael Naumann, Karl-Heinz Smalla, Kerry Tedford, Ulrich Thomas, Anne-Christin Lehmann, Thilo Kähne, Constanze I. Seidenbecher, Dirk Montag, Mark Korthals, Dejan Mamula, Kristina Langnaese, Eckart D. Gundelfinger |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Signal transduction Calcium signalling Science medicine.medical_treatment T cell ATPase Biology Lymphocyte Activation metabolism [Cell Membrane] immunology [T-Lymphocytes] Mice Plasma Membrane Calcium-Transporting ATPases Atp2b1 protein mouse 03 medical and health sciences physiology [Membrane Glycoproteins] 0302 clinical medicine medicine Animals metabolism [Calcium] Calcium Signaling Cell Nucleus Mice Knockout Membrane Glycoproteins Multidisciplinary neuroplastin protein mouse Cell Differentiation physiology [T-Lymphocytes] NFAT Cell biology Mice Inbred C57BL Cytosol 030104 developmental biology Cytokine medicine.anatomical_structure Gene Expression Regulation physiology [Plasma Membrane Calcium-Transporting ATPases] biology.protein Medicine Immunoglobulin superfamily Calcium Neuroplastin ddc:600 030217 neurology & neurosurgery |
| Zdroj: | Scientific Reports, Vol 7, Iss 1, Pp 1-13 (2017) Scientific reports, 7:8358 Scientific reports 7(1), 8358 (2017). doi:10.1038/s41598-017-08519-4 |
| ISSN: | 2045-2322 |
| Popis: | The outcome of T cell activation is determined by mechanisms that balance Ca2+ influx and clearance. Here we report that murine CD4 T cells lacking Neuroplastin (Nptn−/−), an immunoglobulin superfamily protein, display elevated cytosolic Ca2+ and impaired post-stimulation Ca2+ clearance, along with increased nuclear levels of NFAT transcription factor and enhanced T cell receptor-induced cytokine production. On the molecular level, we identified plasma membrane Ca2+ ATPases (PMCAs) as the main interaction partners of Neuroplastin. PMCA levels were reduced by over 70% in Nptn−/− T cells, suggesting an explanation for altered Ca2+ handling. Supporting this, Ca2+ extrusion was impaired while Ca2+ levels in internal stores were increased. T cells heterozygous for PMCA1 mimicked the phenotype of Nptn−/− T cells. Consistent with sustained Ca2+ levels, differentiation of Nptn−/− T helper cells was biased towards the Th1 versus Th2 subset. Our study thus establishes Neuroplastin-PMCA modules as important regulators of T cell activation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|