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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...
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Clathrin-coated vesicles use endocytosis to transport receptors and lysosomal hydrolases from the Golgi to the lysosome in the late secretory pathway. Clathrin-mediated endocytosis was the first described endocytic process, and Clathrin-coated vesicles remain one of the most well-studied transport vesicles. The molecular machinery that generates clathrin-coated vesicles comprises over 50 proteins that precisely coordinate vesicle formation. Cell surface receptors concentrated in indented sites...
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Related Experiment Video

Updated: May 15, 2026

Analysis of Transforming Growth Factor ß Family Cleavage Products Secreted Into the Blastocoele of Xenopus laevis Embryos
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Analysis of Transforming Growth Factor ß Family Cleavage Products Secreted Into the Blastocoele of Xenopus laevis Embryos

Published on: July 21, 2021

Who decides when to cleave an ectodomain?

Monika Hartmann1, Andreas Herrlich, Peter Herrlich

  • 1Leibniz Institute for Age Research - Fritz Lipmann Institute, Herrlich Laboratory, Beutenbergstr. 11, 07745 Jena, Germany.

Trends in Biochemical Sciences
|January 10, 2013
PubMed
Summary

Ectodomain cleavage by ADAM proteases is vital for cell function and linked to disease. Regulation likely involves controlling substrate availability, not just enzyme activity, due to numerous substrates.

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background:

  • Ectodomain cleavage releases essential molecules like growth factors and cytokines.
  • Dysregulation of ectodomain cleavage is implicated in various diseases.
  • Transmembrane ADAMs (a disintegrin and metalloprotease) and other metalloproteases mediate ectodomain cleavage.

Purpose of the Study:

  • To investigate the regulatory mechanisms of ectodomain cleavage.
  • To propose that substrate availability and susceptibility are key regulatory factors.
  • To address the specificity challenge given the excess of substrates over enzymes.

Main Methods:

  • Focus on the regulatory pathways controlling substrate availability.
  • Analysis of substrate accessibility and modification.
  • Comparative study of enzyme-substrate interactions.

Main Results:

  • The number of known substrates for ectodomain cleavage significantly exceeds the number of enzymes.
  • Solely modulating enzyme activity cannot account for the specificity of ectodomain cleavage.
  • Evidence suggests regulatory pathways controlling substrate availability are crucial.

Conclusions:

  • Specificity in ectodomain cleavage is achieved through regulation of substrate availability and susceptibility.
  • Future research should explore these specific regulatory pathways.
  • Understanding these mechanisms is critical for therapeutic interventions in diseases linked to misregulated cleavage.