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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alternative Splicing / genetics*
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Animals
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CD4-Positive T-Lymphocytes / immunology*
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Caspases / genetics*
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Caspases / metabolism
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Down-Regulation
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Enzyme Activation
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Exons / genetics
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HEK293 Cells
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Heterogeneous-Nuclear Ribonucleoprotein U / metabolism
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Humans
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Interleukin-2 / biosynthesis
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JNK Mitogen-Activated Protein Kinases / metabolism
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Jurkat Cells
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Lymphocyte Activation / immunology*
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Mice, Inbred C57BL
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Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
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NF-kappa B / metabolism
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Neoplasm Proteins / genetics*
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Neoplasm Proteins / metabolism
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Receptors, Antigen, T-Cell / metabolism
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Signal Transduction*
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TNF Receptor-Associated Factor 6 / metabolism
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Th17 Cells / immunology
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Up-Regulation
Substances
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Heterogeneous-Nuclear Ribonucleoprotein U
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Interleukin-2
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NF-kappa B
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Neoplasm Proteins
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Receptors, Antigen, T-Cell
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TNF Receptor-Associated Factor 6
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JNK Mitogen-Activated Protein Kinases
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Caspases
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MALT1 protein, human
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Malt1 protein, mouse
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Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein