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

doi:10.1038/ncomms11292

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

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83 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 language	English
Article number	11292
Journal	Nature Communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms11292
State	Published - 12 Apr 2016
Externally published	Yes

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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. (2016). Alternative splicing of MALT1 controls signalling and activation of CD4 + T cells. Nature Communications, 7, Article 11292. https://doi.org/10.1038/ncomms11292

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title = "Alternative splicing of MALT1 controls signalling and activation of CD4 + T cells",

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.",

author = "Isabel Meininger and Griesbach, {Richard A.} and Desheng Hu and Torben Gehring and Thomas Seeholzer and Arianna Bertossi and Jan Kranich and Andrea Oeckinghaus and Eitelhuber, {Andrea C.} and Ute Greczmiel and Andreas Gewies and Marc Schmidt-Supprian and J{\"u}rgen Ruland and Thomas Brocker and Vigo Heissmeyer and Florian Heyd and Daniel Krappmann",

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Meininger, I, Griesbach, RA, Hu, D, Gehring, T, Seeholzer, T, Bertossi, A, Kranich, J, Oeckinghaus, A, Eitelhuber, AC, Greczmiel, U, Gewies, A, Schmidt-Supprian, M, Ruland, J, Brocker, T, Heissmeyer, V, Heyd, F & Krappmann, D 2016, 'Alternative splicing of MALT1 controls signalling and activation of CD4 + T cells', Nature Communications, vol. 7, 11292. https://doi.org/10.1038/ncomms11292

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T1 - Alternative splicing of MALT1 controls signalling and activation of CD4 + T cells

AU - Meininger, Isabel

AU - Griesbach, Richard A.

AU - Hu, Desheng

AU - Gehring, Torben

AU - Seeholzer, Thomas

AU - Bertossi, Arianna

AU - Kranich, Jan

AU - Oeckinghaus, Andrea

AU - Eitelhuber, Andrea C.

AU - Greczmiel, Ute

AU - Gewies, Andreas

AU - Schmidt-Supprian, Marc

AU - Ruland, Jürgen

AU - Brocker, Thomas

AU - Heissmeyer, Vigo

AU - Heyd, Florian

AU - Krappmann, Daniel

PY - 2016/4/12

Y1 - 2016/4/12

N2 - 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.

AB - 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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SN - 2041-1723

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JO - Nature Communications

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

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