Cis-interactions between Notch and its ligands block ligand-independent Notch activity

The Notch pathway is integrated into numerous developmental processes and therefore is fine-tuned on many levels, including receptor production, endocytosis, and degradation. Notch is further characterized by a twofold relationship with its Delta-Serrate (DSL) ligands, as ligands from opposing cells...

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Bibliographic Details
Published in:eLife 2014-12, Vol.3
Main Authors: Palmer, William Hunt, Jia, Dongyu, Deng, Wu-Min
Format: Article
Language:English
Subjects:
Animals
Base Sequence
Cell Biology
Cloning
Developmental Biology and Stem Cells
DNA Primers
Drosophila
Endocytosis
Insects
Ligands
Notch pathway
Notch protein
Oogenesis
Plasmids
Protein Binding
Receptors, Notch - genetics
Receptors, Notch - metabolism
RNA Interference
Short Report
signal transduction
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Summary:The Notch pathway is integrated into numerous developmental processes and therefore is fine-tuned on many levels, including receptor production, endocytosis, and degradation. Notch is further characterized by a twofold relationship with its Delta-Serrate (DSL) ligands, as ligands from opposing cells (trans-ligands) activate Notch, whereas ligands expressed in the same cell (cis-ligands) inhibit signaling. We show that cells without both cis- and trans-ligands can mediate Notch-dependent developmental events during Drosophila oogenesis, indicating ligand-independent Notch activity occurs when the receptor is free of cis- and trans-ligands. Furthermore, cis-ligands can reduce Notch activity in endogenous and genetically induced situations of elevated trans-ligand-independent Notch signaling. We conclude that cis-expressed ligands exert their repressive effect on Notch signaling in cases of trans-ligand-independent activation, and propose a new function of cis-inhibition which buffers cells against accidental Notch activity.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.04415