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Related Concept Videos

Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

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Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
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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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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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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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Paracrine signaling allows cells to communicate with their immediate neighbors via secretion of signaling molecules. Such a signal can only trigger a response in nearby target cells because the signal molecules degrade quickly or are inactivated if not taken up. Prominent examples of paracrine signaling include nitric oxide signaling in blood vessels, synaptic signaling of neurons, the blood clotting system, tissue repair/wound healing, and local allergic skin reactions. Nitric oxide as a...
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Unraveling Key Players of Humoral Immunity: Advanced and Optimized Lymphocyte Isolation Protocol from Murine Peyer's Patches
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Phase separation in immune signalling.

Qian Xiao1, Ceara K McAtee2, Xiaolei Su3,4

  • 1Department of Cell Biology, Yale School of Medicine, New Haven, CT, USA.

Nature Reviews. Immunology
|July 7, 2021
PubMed
Summary

Liquid-liquid phase separation drives the formation of immune signaling condensates. This biophysical process organizes molecules into signaling clusters, offering new insights into immune responses and infection resolution.

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Area of Science:

  • Immunology
  • Biophysics
  • Cell Biology

Background:

  • Immune signaling pathways convert pathogen stimuli into cellular events for infection resolution.
  • Immune receptor activation involves conformational changes and spatial reorganization, forming signaling clusters.
  • Understanding the formation and function of these large, heterogeneous signaling clusters is challenging.

Purpose of the Study:

  • To review the role of liquid-liquid phase separation in forming immune signaling condensates.
  • To explore how phase separation regulates key immune signaling pathways.
  • To highlight current challenges and future research directions in this emerging field.

Main Methods:

  • Literature review of recent studies on phase separation in immunology.
  • Analysis of signaling pathways regulated by liquid-liquid phase separation.
  • Discussion of biophysical principles governing condensate formation.

Main Results:

  • Liquid-liquid phase separation is a key mechanism driving the formation of signaling condensates.
  • These condensates act as signaling hubs, regulating pathways downstream of T cell receptor, B cell receptor, cGAS-STING, and RIG-I.
  • Phase separation provides a fluidic organization for efficient signal transduction.

Conclusions:

  • Liquid-liquid phase separation offers a novel biophysical framework for understanding immune signaling.
  • Further research is needed to fully elucidate the mechanisms and functional consequences of phase separation in immunity.
  • This field holds promise for new perspectives on immune responses and therapeutic strategies.