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, Daniel Krappmann

Research output: Contribution to journalArticlepeer-review

82 Scopus citations

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.

Original languageEnglish
Article number11292
JournalNature Communications
Volume7
DOIs
StatePublished - 12 Apr 2016
Externally publishedYes

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