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Related Concept Videos

Diversity in Cell Signaling Responses01:22

Diversity in Cell Signaling Responses

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The physiological function of a cell and cellular communication are outcomes of a range of extrinsic signals, intracellular signaling pathways, and cellular responses. No two cell types express the same repertoire of signaling components. Receptors are highly selective for their cognate ligands, but once activated, they can alter multiple cellular processes such as DNA transcription, protein synthesis, and metabolic activity. 
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Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...
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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.
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The Power of Simplicity: Sea Urchin Embryos as in Vivo Developmental Models for Studying Complex Cell-to-cell Signaling Network Interactions
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How the Structure of Signaling Regulation Evolves: Insights From an Evolutionary Model.

Danial Asgari1,2, Ann T Tate1,2

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PubMed
Summary
This summary is machine-generated.

Negative feedback loops (NFLs) in cell signaling evolve differently. Downstream NFLs show more robust evolution due to stringent selection, while upstream NFLs are more adaptable to changing conditions.

Keywords:
downstream regulationmultilevel regulationnegative feedbackupstream regulation

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Area of Science:

  • Evolutionary biology
  • Systems biology
  • Molecular biology

Background:

  • Signaling pathways use negative feedback loops (NFLs) to regulate cellular responses to environmental changes.
  • NFLs can function upstream (reducing input) or downstream (reducing output) of signaling cascades.
  • Downstream NFLs regulate gene expression directly, unlike upstream NFLs involving intermediate proteins.

Purpose of the Study:

  • To test the hypothesis that downstream NFLs evolve under more stringent selection than upstream NFLs.
  • To investigate the evolutionary dynamics and robustness of different NFL architectures.
  • To understand the factors influencing the evolution of NFLs in signaling pathways.

Main Methods:

  • Developed a minimal model of immune signaling.
  • Analyzed the evolutionary rates of genes encoding upstream and downstream NFLs.
  • Simulated the evolution of NFLs under varying model parameters, including signaling cost and protein half-life.

Main Results:

  • Genes encoding downstream NFLs evolve at a slower, more consistent rate, indicating stronger selective pressure.
  • Upstream NFLs evolve more rapidly and variably, suggesting weaker or context-specific selection.
  • The number of signaling steps to activate a downstream NFL is influenced by the cost of signaling.
  • Model predicts upstream NFLs favor shorter protein half-lives, absence of co-evolution, and high infection rates.

Conclusions:

  • Downstream NFLs exhibit more robust evolutionary trajectories compared to upstream NFLs.
  • Evolutionary pressures on NFLs are influenced by signaling pathway architecture and environmental factors.
  • Findings provide insights into the evolution of regulatory mechanisms in biological signaling.