Ubiquitylation-independent activation of Notch signalling by Delta
- Heinrich-Heine-Universität Düsseldorf, Germany
- 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.
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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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Ubiquitylation-independent activation of Notch signalling by Delta
eLife 6:e27346.
https://doi.org/10.7554/eLife.27346
