Related Experiment Video

Updated: May 2, 2026

Monitoring Activation of the Antiviral Pattern Recognition Receptors RIG-I And PKR By Limited Protease Digestion and Native PAGE
12:43

Monitoring Activation of the Antiviral Pattern Recognition Receptors RIG-I And PKR By Limited Protease Digestion and Native PAGE

Published on: July 29, 2014

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Prion-like polymerization underlies signal transduction in antiviral immune defense and inflammasome activation

Xin Cai1, Jueqi Chen1, Hui Xu2

  • 1Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Cell
|March 18, 2014
PubMed

Insights

Immune sensors RIG-I and NLRP3 utilize prion-like protein polymerization for signal transduction. This conserved mechanism, involving CARD and PYRIN domains, is crucial for innate immunity and inflammation responses.

Area of Science:

  • Immunology
  • Cellular Biology
  • Biochemistry

Background:

  • Pathogens and danger signals activate immune sensors like RIG-I and NLRP3.
  • These sensors use adaptor proteins MAVS and ASC, containing CARD and PYRIN domains, to trigger immune responses.
  • The precise mechanism of signal transduction by these domains was not fully understood.

Purpose of the Study:

  • To investigate the functional role of CARD and PYRIN domains in innate immune signaling.
  • To determine if prion-like behavior contributes to immune and inflammatory responses.
  • To explore the conservation of this mechanism across species.

Main Methods:

  • Yeast prion assays to assess CARD and PYRIN domain behavior.
  • Mammalian cell signaling experiments to evaluate functional replacement and mutation effects.
  • Biochemical analysis of PYRIN fiber formation and ASC polymerization.

Main Results:

  • CARD and PYRIN domains function as prions in yeast, inducible by upstream activators.
  • Yeast prion domains can substitute for CARD and PYRIN in mammalian cell signaling.
  • Mutations affecting prion activity in yeast also impair mammalian signaling.
  • Recombinant PYRIN induces ASC polymerization and caspase-1 activation.
  • A fungal prion-receptor pair reconstitutes mammalian NLRP3/ASC signaling.

Conclusions:

  • Prion-like polymerization is a conserved mechanism for signal transduction in innate immunity and inflammation.
  • This finding offers new insights into the regulation of immune responses.
  • The study highlights a novel role for prions beyond neurodegenerative diseases.

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