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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

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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.
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Feedback control systems are categorized in various ways based on their design, analysis, and signal types.
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Open and closed-loop control systems01:17

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Control systems are foundational elements in automation and engineering. They are broadly categorized into open-loop and closed-loop systems. These classifications hinge on the presence or absence of feedback mechanisms, significantly influencing the system's performance, complexity, and application.
An open-loop control system operates without feedback from the output. It consists of two primary elements: the controller and the controlled process. The controller receives an input signal...
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Control Systems01:10

Control Systems

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Control systems are everywhere in contemporary society, influencing diverse applications from aerospace to automated manufacturing. These systems can be found naturally within biological processes, such as blood sugar regulation and heart rate adjustment in response to stress, as well as in man-made systems like elevators and automated vehicles. A control system is essentially a network of subsystems and processes that collaboratively convert specific inputs into desired outputs.
At the heart...
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¹H NMR: Interpreting Distorted and Overlapping Signals01:02

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Spin systems where the difference in chemical shifts of the coupled nuclei is greater than ten times J are called first-order spin systems. These nuclei are weakly coupled, and their chemical shifts and coupling constant can generally be estimated from the well-separated signals in the spectrum.
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Synthetic, Multi-Layer, Self-Oscillating Vocal Fold Model Fabrication
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Functional Comparison between Endogenous and Synthetic Notch Systems.

Bassma Khamaisi1, Vincent C Luca2, Stephen C Blacklow3

  • 1George S. Wise Faculty of Life Sciences, School of Neurobiology, Biochemistry, and Biophysics, Tel Aviv University, Tel Aviv 69978, Israel.

ACS Synthetic Biology
|September 15, 2022
PubMed
Summary
This summary is machine-generated.

Synthetic Notch (synNotch) systems engineered with antibody-antigen interactions bypass the need for a ligand intracellular domain (ICD) for activation. This occurs because antigen-antibody binding promotes cell adhesion and mechanical tension, unlike other synNotch systems or endogenous Notch signaling.

Keywords:
EGF repeatsNotch signalingendocytosismembrane proteinssynNotchtrans-endocytosis

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Area of Science:

  • Cellular signaling
  • Synthetic biology
  • Molecular mechanisms

Background:

  • The Notch pathway is crucial for cell-cell communication, translating surface interactions into transcriptional changes.
  • Synthetic Notch (synNotch) systems have been engineered to respond to diverse inputs and elicit specific cellular outputs.
  • A key synNotch class utilizes antibody-antigen interactions, converting surface antigen recognition into a cellular response via receptor cleavage.

Purpose of the Study:

  • To investigate the mechanism underlying synNotch activation, specifically the role of the ligand intracellular domain (ICD).
  • To compare the activation requirements of antibody-antigen synNotch (aa-synNotch) with endogenous Notch and a rapamycin-inducible synNotch (ff-synNotch).
  • To elucidate factors influencing the dependence of Notch and synNotch systems on ligand ICD.

Main Methods:

  • Comparative analysis of aa-synNotch, endogenous Notch, and ff-synNotch activation mechanisms.
  • Investigation of structural and biochemical factors, including receptor-ligand affinity, transmembrane domains, and extracellular domains.
  • Assessment of trans-endocytosis of receptor extracellular domains in different synNotch systems.

Main Results:

  • Unlike endogenous Notch and ff-synNotch, aa-synNotch activation does not require a ligand ICD.
  • Differences in receptor-ligand affinity, transmembrane domains, or extracellular domains do not explain the lack of ICD dependence in aa-synNotch.
  • aa-synNotch systems do not exhibit trans-endocytosis, suggesting an alternative activation mechanism.

Conclusions:

  • The aa-synNotch system bypasses the ligand ICD requirement through antigen-antibody interactions.
  • Cellular adhesion and mechanical tension generated by antigen-antibody pairs are key to aa-synNotch activation.
  • These findings challenge existing models of synNotch activation and highlight the importance of mechanical forces in signaling.