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Related Concept Videos

Notch Signaling Pathway03:14

Notch Signaling Pathway

4.3K
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...
4.3K
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

2.1K
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...
2.1K
Mechanism of Filopodia Formation01:39

Mechanism of Filopodia Formation

2.3K
Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
2.3K
Mechanism of Lamellipodia Formation01:31

Mechanism of Lamellipodia Formation

2.6K
Cells migrating in response to external stimuli form lamellipodia, which are thin membrane protrusions supported by a mesh of linked, branched, or unbranched actin filaments. These actin filaments interact with myosin motor proteins, creating the dynamic actomyosin complex within the cytoskeleton. Contractility, or the ability to generate contractile stress, is inherent to the actomyosin complex. It helps cells detect the stiffness of the surrounding ECM and exert contractile force for...
2.6K
Tension Response at Adherens Junctions01:26

Tension Response at Adherens Junctions

2.6K
The adherens junctions that anchor cells together are multi-protein complexes that dynamically adapt to mechanical stimuli such as tensile forces and shear stress. Mechanosensory proteins in these junctions can sense such mechanical stimuli and undergo a shift in their conformation, resulting in an altered function — a process called mechanotransduction.
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin...
2.6K
Single-Strand DNA Binding Proteins01:03

Single-Strand DNA Binding Proteins

14.1K
For successful DNA replication, the unwinding of double-stranded DNA must be accompanied by stabilization and protection of the separated single strands of the DNA. This crucial task is performed by single-strand DNA-binding (SSB) proteins. They bind to the DNA in a sequence-independent manner, which means that the nitrogenous bases of the DNA need not be present in a specific order for binding of SSB proteins to it. The binding of SSB proteins straightens single-stranded DNA (ssDNA) and makes...
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Related Experiment Video

Updated: Jul 5, 2025

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

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Soluble and multivalent Jag1 DNA origami nanopatterns activate Notch without pulling force.

Ioanna Smyrlaki1, Ferenc Fördős1, Iris Rocamonde-Lago1

  • 1Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.

Nature Communications
|January 18, 2024
PubMed
Summary

Notch signaling activation can occur without pulling forces, challenging current models. This discovery, using precise ligand nanopatterns, reveals a new activation mechanism and potential for soluble agonists.

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DNA Origami-Mediated Substrate Nanopatterning of Inorganic Structures for Sensing Applications
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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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Cell Aggregation Assays to Evaluate the Binding of the Drosophila Notch with Trans-Ligands and its Inhibition by Cis-Ligands

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Last Updated: Jul 5, 2025

Stimulation of Notch Signaling in Mouse Osteoclast Precursors
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DNA Origami-Mediated Substrate Nanopatterning of Inorganic Structures for Sensing Applications
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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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Cell Aggregation Assays to Evaluate the Binding of the Drosophila Notch with Trans-Ligands and its Inhibition by Cis-Ligands

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Area of Science:

  • Cellular signaling pathways
  • Developmental biology
  • Neuroscience

Background:

  • The Notch signaling pathway is crucial for embryonic development and nervous system function.
  • Current models propose receptor activation relies on force-induced conformational changes.

Purpose of the Study:

  • To investigate Notch signaling activation independent of pulling forces.
  • To explore alternative mechanisms of Notch activation using soluble multivalent constructs.

Main Methods:

  • Utilized DNA origami to create precise ligand nanopatterns displayed from solution.
  • Treated neuroepithelial stem-like cells with these nanopatterns, including Jag1 clusters and chimeric structures.
  • Analyzed Notch signaling activation under these conditions.

Main Results:

  • Demonstrated Notch signaling activation without requiring pulling forces.
  • Identified prolonged binding as a key factor in activation, even with modified ligand structures.
  • Ruled out several potential confounding factors in the experimental setup.

Conclusions:

  • Proposed a novel model for Notch activation involving prolonged ligand binding, independent of mechanical force.
  • Established conditions for force-independent Notch activation, challenging existing paradigms.
  • Laid the groundwork for developing novel soluble Notch agonists.