A complex of Neuroplastin and Plasma Membrane Ca2+ ATPase controls T cell activation

Thomas, Ulrich; Naumann, Michael; Korthals, Mark; Seidenbecher, Constanze; Smalla, Karl-Heinz; Zuschratter, Werner; Herrera-Molina, Rodrigo; Tedford, Kerry; Lehmann, Anne-Christin; Gundelfinger, Eckart D.; Langnaese, Kristina; Montag, Dirk; Handschuh, Juliane; Fischer, Klaus-Dieter; Kahne, Thilo; et. al.


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.

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Título según WOS: ID WOS:000408102500033 Not found in local WOS DB
Título de la Revista: SCIENTIFIC REPORTS
Volumen: 7
Editorial: Nature Publishing Group
Fecha de publicación: 2017


Notas: ISI