Alternative Splicing of MALT1 Controls Signalling and Activation of CD4(+) T Cells

Overview

Journal Nat Commun

Specialty Biology

Date 2016 Apr 13

PMID 27068814

Citations 54

Authors

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

Jurgen Ruland

Thomas Brocker

Vigo Heissmeyer

Florian Heyd

Daniel Krappmann

Affiliations

Soon will be listed here.

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.

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