PuSH - Publikationsserver des Helmholtz Zentrums München: Alternative splicing of MALT1 controls signalling and activation of CD4<sup>+</sup> T cells.

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Meininger, I. ; Griesbach, R.A. ; Hu, D. ; Gehring, T. ; Seeholzer, T. ; Bertossi, A. ; Kranich, J.* ; Oeckinghaus, A. ; Eitelhuber, A.C. ; Greczmiel, U. ; Gewies, A.* ; Schmidt-Supprian, M.* ; Ruland, J.* ; Brocker, T.* ; Heissmeyer, V. ; Heyd, F.* ; Krappmann, D.

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

Nat. Commun. 7:11292 (2016)

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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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PuSH - Publikationsserver des Helmholtz Zentrums München

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

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