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Related Concept Videos

Notch Signaling Pathway03:14

Notch Signaling Pathway

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 until 1985...
Notch Signaling Pathway03:14

Notch Signaling Pathway

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 until 1985...
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

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...
Restarting Stalled Replication Forks02:37

Restarting Stalled Replication Forks

DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart, a...
Catenins01:23

Catenins

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
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the adherens...
Cadherins in Tissue Organization01:19

Cadherins in Tissue Organization

The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
Cell sorting plays an...

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Related Experiment Video

Updated: Jun 23, 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

CADASIL mutations enhance spontaneous multimerization of NOTCH3.

Christian Opherk1, Marco Duering, Nils Peters

  • 1Department of Neurology, Ludwig-Maximilians-University, Munich, Germany.

Human Molecular Genetics
|May 7, 2009
PubMed
Summary

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is linked to mutations in the NOTCH3 receptor. These mutations enhance the self-association of the NOTCH3 extracellular domain, leading to its accumulation and cell degeneration.

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Stimulation of Notch Signaling in Mouse Osteoclast Precursors
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Stimulation of Notch Signaling in Mouse Osteoclast Precursors

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Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
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Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer

Published on: January 12, 2020

Related Experiment Videos

Last Updated: Jun 23, 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

Stimulation of Notch Signaling in Mouse Osteoclast Precursors
08:01

Stimulation of Notch Signaling in Mouse Osteoclast Precursors

Published on: February 28, 2017

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
09:08

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer

Published on: January 12, 2020

Area of Science:

  • Neuroscience
  • Genetics
  • Biochemistry

Background:

  • Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the leading monogenic cause of stroke and vascular dementia.
  • Mutations causing CADASIL occur in the NOTCH3 receptor's extracellular domain (N3(ECD)), specifically affecting cysteine residues.
  • A key feature of CADASIL is the accumulation of N3(ECD) on vascular smooth muscle cells, leading to their degeneration, but the underlying mechanism is unknown.

Purpose of the Study:

  • To investigate the molecular mechanisms behind N3(ECD) accumulation in CADASIL.
  • To determine if N3(ECD) undergoes self-association and if CADASIL mutations influence this process.

Main Methods:

  • In vitro analysis of wild-type and CADASIL-mutated N3(ECD) multimerization.
  • Utilized scanning for intensely fluorescent targets (SIFT) single-molecule analysis techniques.
  • Investigated the role of disulfide bonds in N3(ECD) multimerization.

Main Results:

  • Both wild-type and CADASIL-mutated N3(ECD) spontaneously form oligomers and multimers in vitro.
  • Multimerization is mediated by disulfide bonds.
  • CADASIL mutations significantly enhance N3(ECD) multimerization compared to the wild-type receptor.

Conclusions:

  • This study provides the first experimental evidence for NOTCH3 receptor self-association.
  • CADASIL-associated mutations appear to induce a neomorphic effect, promoting N3(ECD) multimerization and contributing to disease pathogenesis.