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Related Concept Videos

Notch Signaling Pathway03:14

Notch Signaling Pathway

6.8K
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
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Notch Signaling Pathway03:14

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Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

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Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
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Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

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Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
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Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

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Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
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Catenins01:23

Catenins

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Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
Catenins in Cell Junctions
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Related Experiment Video

Updated: Mar 12, 2026

Cell Aggregation Assays to Evaluate the Binding of the Drosophila Notch with Trans-Ligands and its Inhibition by Cis-Ligands
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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NOTCH3 CADASIL Variant Receptor Aggregation Requires NOTCH3 Wild-Type Receptors: Identification of Highly Selective

Haijiang Wang1,2, Xinxin Liu2, Gido Gravesteijn3

  • 1Department of General Surgery, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|March 10, 2026
PubMed
Summary
This summary is machine-generated.

Cerebral autosomal dominant arteriopathy with subcortical infarctions and leukoencephalopathy (CADASIL) is caused by NOTCH3 mutations. Pathogenic variants promote NOTCH3 receptor aggregation and enhance signaling, offering a target for new therapies.

Keywords:
CADASILNOTCH receptor inhibitorsNOTCH signalingpeptide‐based inhibitorsprotein aggregationtargeted therapy

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Last Updated: Mar 12, 2026

Cell Aggregation Assays to Evaluate the Binding of the Drosophila Notch with Trans-Ligands and its Inhibition by Cis-Ligands
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Cell Aggregation Assays to Evaluate the Binding of the Drosophila Notch with Trans-Ligands and its Inhibition by Cis-Ligands

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Stimulation of Notch Signaling in Mouse Osteoclast Precursors
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Measuring Transcellular Interactions through Protein Aggregation in a Heterologous Cell System
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Measuring Transcellular Interactions through Protein Aggregation in a Heterologous Cell System

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Area of Science:

  • Neuroscience
  • Genetics
  • Molecular Biology

Background:

  • Cerebral autosomal dominant arteriopathy with subcortical infarctions and leukoencephalopathy (CADASIL) is a genetic small vessel disease.
  • It causes strokes, cognitive decline, and dementia due to NOTCH3 gene mutations.
  • The exact molecular mechanisms of NOTCH3 mutations in CADASIL are not fully understood.

Purpose of the Study:

  • To investigate the impact of pathogenic NOTCH3 variants on receptor aggregation and signaling.
  • To elucidate the molecular mechanisms underlying CADASIL pathogenesis.

Main Methods:

  • Biochemical analysis of NOTCH3 receptor aggregation using in vitro and cell-based assays.
  • Investigating the interaction between mutant NOTCH3 receptors and wild-type receptors.
  • Assessing the effect of pathogenic variants on JAGGED1-dependent NOTCH3 transactivation.

Main Results:

  • CADASIL mutant NOTCH3 receptors do not aggregate independently but promote aggregation with wild-type receptors.
  • Pathogenic NOTCH3 variants at EGFr 4 significantly enhance JAGGED1-dependent NOTCH3 signaling.
  • Paralogue-specific NOTCH3 inhibitors can block receptor aggregation and signaling.

Conclusions:

  • NOTCH3 receptor aggregation and enhanced signaling are key mechanisms in CADASIL.
  • Targeting NOTCH3 receptor aggregation and signaling with specific inhibitors presents a potential therapeutic strategy.
  • This study provides insights into the molecular basis of CADASIL and potential treatment avenues.