Alternative splicing of MALT1 controls signalling and activation of CD4+ T cells

Isabel Meininger, Richard A. Griesbach, Desheng Hu, Torben Gehring, Thomas Seeholzer, Arianna Bertossi, Jan Kranich, Andrea Oeckinghaus, Andrea C. Eitelhuber, Ute Greczmiel, Andreas Gewies, Marc Schmidt-Supprian, Jürgen Ruland, Thomas Brocker, Vigo Heissmeyer, Florian Heyd and Daniel Krappmann ()
Additional contact information
Isabel Meininger: Research Unit Cellular Signal Integration, Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München—German Research Center for Environmental Health
Richard A. Griesbach: Research Unit Cellular Signal Integration, Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München—German Research Center for Environmental Health
Desheng Hu: Research Unit Molecular Immune Regulation, Helmholtz Zentrum München—German Research Center for Environmental Health
Torben Gehring: Research Unit Cellular Signal Integration, Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München—German Research Center for Environmental Health
Thomas Seeholzer: Research Unit Cellular Signal Integration, Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München—German Research Center for Environmental Health
Arianna Bertossi: Research Unit Cellular Signal Integration, Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München—German Research Center for Environmental Health
Jan Kranich: Institute for Immunology, Biomedical Center Munich, LMU Munich
Andrea Oeckinghaus: Research Unit Cellular Signal Integration, Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München—German Research Center for Environmental Health
Andrea C. Eitelhuber: Research Unit Cellular Signal Integration, Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München—German Research Center for Environmental Health
Ute Greczmiel: Research Unit Cellular Signal Integration, Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München—German Research Center for Environmental Health
Andreas Gewies: Institut für Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar, Technische Universität München
Marc Schmidt-Supprian: German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ)
Jürgen Ruland: Institut für Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar, Technische Universität München
Thomas Brocker: Institute for Immunology, Biomedical Center Munich, LMU Munich
Vigo Heissmeyer: Research Unit Molecular Immune Regulation, Helmholtz Zentrum München—German Research Center for Environmental Health
Florian Heyd: Free University Berlin, Institute of Chemistry and Biochemistry, RNA Biochemistry
Daniel Krappmann: Research Unit Cellular Signal Integration, Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München—German Research Center for Environmental Health

Nature Communications, 2016, vol. 7, issue 1, 1-15

Abstract: Abstract MALT1 channels proximal T-cell receptor (TCR) signalling to downstream signalling pathways. With MALT1A and MALT1B two conserved splice variants exist and we demonstrate here that MALT1 alternative splicing supports optimal T-cell activation. Inclusion of exon7 in MALT1A facilitates the recruitment of TRAF6, which augments MALT1 scaffolding function, but not protease activity. Naive CD4+ T cells express almost exclusively MALT1B and MALT1A expression is induced by TCR stimulation. We identify hnRNP U as a suppressor of exon7 inclusion. Whereas selective depletion of MALT1A impairs T-cell signalling and activation, downregulation of hnRNP U enhances MALT1A expression and T-cell activation. Thus, TCR-induced alternative splicing augments MALT1 scaffolding to enhance downstream signalling and to promote optimal T-cell activation.

Date: 2016
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11292

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DOI: 10.1038/ncomms11292

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