OptIC-Notch reveals mechanism that regulates receptor interactions with CSL

Related Experiment Video

Updated: Jul 27, 2025

An Optogenetic Method to Control and Analyze Gene Expression Patterns in Cell-to-cell Interactions
07:59

An Optogenetic Method to Control and Analyze Gene Expression Patterns in Cell-to-cell Interactions

Published on: March 22, 2018

7.8K

Jonathan M Townson1, Maria J Gomez-Lamarca1, Carmen Santa Cruz Mateos1

  • 1Department of Physiology Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.

Development (Cambridge, England)
|June 9, 2023
PubMed

Insights

Optogenetic control of Notch signaling reveals that the Notch intracellular domain (NICD) sequesters the CSL protein in the cytoplasm until released by light. This light-induced release facilitates CSL nuclear import and target gene activation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Notch signaling is crucial for development and disease, involving receptor-ligand interactions and the release of the Notch intracellular domain (NICD).
  • NICD forms a transcriptional complex with CSL (CBF1/Su(H)/LAG-1) and Mastermind, but the site of complex formation remains unclear as CSL lacks a nuclear localization sequence.

Purpose of the Study:

  • To investigate the mechanisms of Notch-CSL complex formation and target gene activation using a novel optogenetic approach.
  • To determine the role of NICD release and CSL sequestration in the cytoplasm.

Main Methods:

  • Development of an optogenetic tool (OptIC-Notch) to control NICD release via light.
  • Monitoring of CSL localization and tripartite complex formation in response to light-induced NICD release.
  • Analysis of target gene expression following controlled NICD release.

Main Results:

  • Uncleaved OptIC-Notch sequesters CSL in the cytoplasm, dependent on a juxtamembrane ΦWΦP motif.
  • Masking the ΦWΦP motif prevents CSL sequestration.
  • Light-induced NICD release from either OptIC-Notch or modified versions efficiently promotes CSL nuclear import and target gene activation.

Conclusions:

  • The exposure of the ΦWΦP motif is critical for CSL sequestration, likely in the cytoplasm.
  • Optogenetic control of NICD release provides a powerful tool to study Notch signaling dynamics.
  • Notch-CSL complex formation can initiate in the cytoplasm prior to nuclear entry.
Keywords:
DrosophilaCSLNotchNuclear translocationOptogenetics

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