Ubiquitylation-independent activation of Notch signalling by Delta

  1. Nicole Berndt
  2. Ekaterina Seib
  3. Soya Kim
  4. Tobias Troost
  5. Marvin Lyga
  6. Jessica Langenbach
  7. Sebastian Haensch
  8. Konstantina Kalodimou
  9. Christos Delidakis
  10. Thomas Klein  Is a corresponding author
  1. Heinrich-Heine-Universität Düsseldorf, Germany
  2. Foundation for Research and Technology - Hellas, Greece

Abstract

Ubiquitylation (ubi) through the E3-ligases Mindbomb1 (Mib1) and Neuralized (Neur) is required for activation of the DSL ligands Delta (Dl) and Serrate (Ser) to activate Notch signalling. These ligases transfer ubiquitin to lysines of the ligands' intracellular domains (ICDs), which sends them into an Epsin-dependent endocytic pathway. Here, we have tested the requirement of ubi of Dl for signalling. We found that Dl requires ubi for its full function, but can also signal in two ubi-independent modes, one dependent and one independent of Neur. We identified two neural lateral specification processes where Dl signals in an ubi-independent manner. Neur, which is needed for these processes, was shown to be able to activate Dl in an ubi-independent manner. Our analysis suggests that one important role of DSL protein ubi by Mib1 is their release from cis-inhibitory interactions with Notch, enabling them to trans-activate Notch on adjacent cells.

Article and author information

Author details

  1. Nicole Berndt

    Institute of Genetics, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Ekaterina Seib

    Institute of Genetics, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Soya Kim

    Institute of Genetics, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Tobias Troost

    Institute of Genetics, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Marvin Lyga

    Institute of Genetics, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Jessica Langenbach

    Institute of Genetics, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Sebastian Haensch

    Center for Advanced Imaging (CAi), Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany
    Competing interests
    The authors declare that no competing interests exist.
  8. Konstantina Kalodimou

    Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology - Hellas, Heraklion, Greece
    Competing interests
    The authors declare that no competing interests exist.
  9. Christos Delidakis

    Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology - Hellas, Heraklion, Greece
    Competing interests
    The authors declare that no competing interests exist.
  10. Thomas Klein

    Institute of Genetics, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany
    For correspondence
    thomas.klein@hhu.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2719-9617

Funding

Deutsche Forschungsgemeinschaft (KL 1028/3-1)

  • Thomas Klein

Deutsche Forschungsgemeinschaft (SFB 1208 Teilprojekt B01)

  • Thomas Klein

European Cooperation in Science and Technology (BM1307)

  • Christos Delidakis

General Secretariat for Research and Technology (grant No 4436)

  • Christos Delidakis

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2017, Berndt et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Nicole Berndt
  2. Ekaterina Seib
  3. Soya Kim
  4. Tobias Troost
  5. Marvin Lyga
  6. Jessica Langenbach
  7. Sebastian Haensch
  8. Konstantina Kalodimou
  9. Christos Delidakis
  10. Thomas Klein
(2017)
Ubiquitylation-independent activation of Notch signalling by Delta
eLife 6:e27346.
https://doi.org/10.7554/eLife.27346

Share this article

https://doi.org/10.7554/eLife.27346

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