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Updated: May 5, 2026
05:48
Cell Aggregation Assays to Evaluate the Binding of the Drosophila Notch with Trans-Ligands and its Inhibition by Cis-Ligands
Published on: January 2, 2018
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Structural analysis uncovers lipid-binding properties of Notch ligands
Chandramouli R Chillakuri1, Devon Sheppard, Ma Xenia G Ilagan
1Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
Cell Reports
|November 19, 2013
Summary
The Notch pathway
Area of Science:
- Cell signaling
- Molecular biology
- Developmental biology
Background:
- The Notch pathway is crucial for cell-cell communication in multicellular organisms.
- Notch ligands interact with Notch receptors to initiate signaling.
- The N-terminal region of Notch ligands has been uncharacterized despite disease relevance.
Purpose of the Study:
- To investigate the function of the N-terminal domain of Notch ligands.
- To determine the role of this domain in Notch pathway activation.
Main Methods:
- Biochemical assays to assess phospholipid binding.
- Calcium-dependent binding studies.
- Site-directed mutagenesis to probe functional residues.
- Analysis of Notch receptor interactions and activation.
Main Results:
- The N terminus of Jagged-1 functions as a C2 phospholipid-binding domain.
- This domain binds phospholipid bilayers in a calcium-dependent manner.
- This phospholipid-binding activity is conserved in Delta-like-1 and Serrate.
- Mutations in the C2 domain affect Notch activation without disrupting receptor interaction.
Conclusions:
- Phospholipid recognition by Notch ligand N termini is a novel regulatory mechanism.
- This previously unknown function impacts Notch pathway signaling control.
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