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Related Concept Videos

Notch Signaling Pathway03:14

Notch Signaling Pathway

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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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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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MAPK Signaling Cascades01:07

MAPK Signaling Cascades

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Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
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Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

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The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
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Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

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When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
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The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

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Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
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Stimulation of Notch Signaling in Mouse Osteoclast Precursors
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Notch Signaling: Where Is the Action?

Jens Januschke1, Andreas Wodarz2

  • 1Cell & Developmental Biology, School of Life Sciences, University of Dundee, JBC/WBT/MSI Complex, Dundee DD1 5EH, Scotland, UK.

Current Biology : CB
|August 9, 2017
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Summary

Notch ligand activation occurs in specific plasma membrane regions. This study confirms this localization in Drosophila sensory organ precursor cells, answering a long-standing biological question.

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Isolation of Whole Cell Protein Lysates from Mouse Facial Processes and Cultured Palatal Mesenchyme Cells for Phosphoprotein Analysis
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Area of Science:

  • Cell biology
  • Developmental biology
  • Molecular biology

Background:

  • The precise location of cell signaling initiation is crucial for developmental processes.
  • Notch signaling is a fundamental pathway regulating cell fate and differentiation.
  • Previous research has debated whether Notch receptor activation is spatially restricted on the cell surface.

Purpose of the Study:

  • To investigate the spatial dynamics of Notch receptor activation by its ligands.
  • To determine if Notch activation occurs at specific plasma membrane domains.
  • To elucidate the role of membrane localization in Notch signaling within a developmental context.

Main Methods:

  • Utilized live imaging techniques in Drosophila melanogaster.
  • Employed fluorescent reporters to visualize Notch ligand-receptor interactions.
  • Analyzed the spatial distribution of signaling events in sensory organ precursor cells.

Main Results:

  • Demonstrated that Notch ligand binding and subsequent receptor activation are spatially restricted to specific membrane microdomains.
  • Identified distinct regions on the plasma membrane where Notch signaling is initiated.
  • Provided visual evidence of localized signaling events during cell fate determination.

Conclusions:

  • Notch receptor activation is not a random event but is spatially regulated.
  • Specific plasma membrane domains serve as platforms for initiating Notch signaling.
  • This spatial control is critical for the proper development of Drosophila sensory organs.