IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v7y2016i1d10.1038_ncomms11292.html
   My bibliography  Save this article

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

Author

Listed:
  • Isabel Meininger

    (Research Unit Cellular Signal Integration, Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München—German Research Center for Environmental Health)

  • Richard A. Griesbach

    (Research Unit Cellular Signal Integration, Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München—German Research Center for Environmental Health
    Natural and Medical Sciences Institute at the University of Tübingen)

  • Desheng Hu

    (Research Unit Molecular Immune Regulation, Helmholtz Zentrum München—German Research Center for Environmental Health
    Institute for Immunology, Biomedical Center Munich, LMU Munich)

  • Torben Gehring

    (Research Unit Cellular Signal Integration, Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München—German Research Center for Environmental Health)

  • Thomas Seeholzer

    (Research Unit Cellular Signal Integration, Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München—German Research Center for Environmental Health)

  • Arianna Bertossi

    (Research Unit Cellular Signal Integration, Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München—German Research Center for Environmental Health)

  • Jan Kranich

    (Institute for Immunology, Biomedical Center Munich, LMU Munich)

  • Andrea Oeckinghaus

    (Research Unit Cellular Signal Integration, Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München—German Research Center for Environmental Health
    Present address: Institute of Molecular Tumor Biology, University of Münster, Robert-Koch-Straße 43, 48149 Münster, Germany)

  • Andrea C. Eitelhuber

    (Research Unit Cellular Signal Integration, Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München—German Research Center for Environmental Health)

  • Ute Greczmiel

    (Research Unit Cellular Signal Integration, Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München—German Research Center for Environmental Health)

  • Andreas Gewies

    (Institut für Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar, Technische Universität München
    German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ))

  • Marc Schmidt-Supprian

    (German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ)
    Molecular Immunopathology & Signal Transduction, III. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München)

  • Jürgen Ruland

    (Institut für Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar, Technische Universität München
    German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ)
    German Center for Infection Research (DZIF), partner site Munich)

  • Thomas Brocker

    (Institute for Immunology, Biomedical Center Munich, LMU Munich)

  • Vigo Heissmeyer

    (Research Unit Molecular Immune Regulation, Helmholtz Zentrum München—German Research Center for Environmental Health
    Institute for Immunology, Biomedical Center Munich, LMU Munich)

  • Florian Heyd

    (Free University Berlin, Institute of Chemistry and Biochemistry, RNA Biochemistry)

  • Daniel Krappmann

    (Research Unit Cellular Signal Integration, Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München—German Research Center for Environmental Health)

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.

Suggested Citation

  • Isabel Meininger & Richard A. Griesbach & Desheng Hu & Torben Gehring & Thomas Seeholzer & Arianna Bertossi & Jan Kranich & Andrea Oeckinghaus & Andrea C. Eitelhuber & Ute Greczmiel & Andreas Gewies &, 2016. "Alternative splicing of MALT1 controls signalling and activation of CD4+ T cells," Nature Communications, Nature, vol. 7(1), pages 1-15, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11292
    DOI: 10.1038/ncomms11292
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms11292
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms11292?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Weili Wang & Huizhen Zheng & Jun Jiang & Zhi Li & Dongpeng Jiang & Xiangru Shi & Hui Wang & Jie Jiang & Qianqian Xie & Meng Gao & Jianhong Chu & Xiaoming Cai & Tian Xia & Ruibin Li, 2022. "Engineering micro oxygen factories to slow tumour progression via hyperoxic microenvironments," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Timofey A. Karginov & Antoine Ménoret & Anthony T. Vella, 2022. "Optimal CD8+ T cell effector function requires costimulation-induced RNA-binding proteins that reprogram the transcript isoform landscape," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    3. Tamar Sapir & Aditya Kshirsagar & Anna Gorelik & Tsviya Olender & Ziv Porat & Ingrid E. Scheffer & David B. Goldstein & Orrin Devinsky & Orly Reiner, 2022. "Heterogeneous nuclear ribonucleoprotein U (HNRNPU) safeguards the developing mouse cortex," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11292. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.