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

Abstract 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, a...

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Autores principales:	Mark Korthals, Kristina Langnaese, Karl-Heinz Smalla, Thilo Kähne, Rodrigo Herrera-Molina, Juliane Handschuh, Anne-Christin Lehmann, Dejan Mamula, Michael Naumann, Constanze Seidenbecher, Werner Zuschratter, Kerry Tedford, Eckart D. Gundelfinger, Dirk Montag, Klaus-Dieter Fischer, Ulrich Thomas
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d130938189af4ca2b4aea89ebca3139c
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spelling	oai:doaj.org-article:d130938189af4ca2b4aea89ebca3139c2021-12-02T15:05:15ZA complex of Neuroplastin and Plasma Membrane Ca2+ ATPase controls T cell activation10.1038/s41598-017-08519-42045-2322https://doaj.org/article/d130938189af4ca2b4aea89ebca3139c2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08519-4https://doaj.org/toc/2045-2322Abstract 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.Mark KorthalsKristina LangnaeseKarl-Heinz SmallaThilo KähneRodrigo Herrera-MolinaJuliane HandschuhAnne-Christin LehmannDejan MamulaMichael NaumannConstanze SeidenbecherWerner ZuschratterKerry TedfordEckart D. GundelfingerDirk MontagKlaus-Dieter FischerUlrich ThomasNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mark Korthals Kristina Langnaese Karl-Heinz Smalla Thilo Kähne Rodrigo Herrera-Molina Juliane Handschuh Anne-Christin Lehmann Dejan Mamula Michael Naumann Constanze Seidenbecher Werner Zuschratter Kerry Tedford Eckart D. Gundelfinger Dirk Montag Klaus-Dieter Fischer Ulrich Thomas A complex of Neuroplastin and Plasma Membrane Ca2+ ATPase controls T cell activation
description	Abstract 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.
format	article
author	Mark Korthals Kristina Langnaese Karl-Heinz Smalla Thilo Kähne Rodrigo Herrera-Molina Juliane Handschuh Anne-Christin Lehmann Dejan Mamula Michael Naumann Constanze Seidenbecher Werner Zuschratter Kerry Tedford Eckart D. Gundelfinger Dirk Montag Klaus-Dieter Fischer Ulrich Thomas
author_facet	Mark Korthals Kristina Langnaese Karl-Heinz Smalla Thilo Kähne Rodrigo Herrera-Molina Juliane Handschuh Anne-Christin Lehmann Dejan Mamula Michael Naumann Constanze Seidenbecher Werner Zuschratter Kerry Tedford Eckart D. Gundelfinger Dirk Montag Klaus-Dieter Fischer Ulrich Thomas
author_sort	Mark Korthals
title	A complex of Neuroplastin and Plasma Membrane Ca2+ ATPase controls T cell activation
title_short	A complex of Neuroplastin and Plasma Membrane Ca2+ ATPase controls T cell activation
title_full	A complex of Neuroplastin and Plasma Membrane Ca2+ ATPase controls T cell activation
title_fullStr	A complex of Neuroplastin and Plasma Membrane Ca2+ ATPase controls T cell activation
title_full_unstemmed	A complex of Neuroplastin and Plasma Membrane Ca2+ ATPase controls T cell activation
title_sort	complex of neuroplastin and plasma membrane ca2+ atpase controls t cell activation
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/d130938189af4ca2b4aea89ebca3139c
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A complex of Neuroplastin and Plasma Membrane Ca2+ ATPase controls T cell activation

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