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

Xin Cai, Jueqi Chen, Hui Xu, Siqi Liu, Qiu Xing Jiang, Randal Halfmann, Zhijian J. Chen

Research output: Contribution to journalArticle

252 Citations (Scopus)

Abstract

Pathogens and cellular danger signals activate sensors such as RIG-I and NLRP3 to produce robust immune and inflammatory responses through respective adaptor proteins MAVS and ASC, which harbor essential N-terminal CARD and PYRIN domains, respectively. Here, we show that CARD and PYRIN function as bona fide prions in yeast and that their prion forms are inducible by their respective upstream activators. Likewise, a yeast prion domain can functionally replace CARD and PYRIN in mammalian cell signaling. Mutations in MAVS and ASC that disrupt their prion activities in yeast also abrogate their ability to signal in mammalian cells. Furthermore, fibers of recombinant PYRIN can convert ASC into functional polymers capable of activating caspase-1. Remarkably, a conserved fungal NOD-like receptor and prion pair can functionally reconstitute signaling of NLRP3 and ASC PYRINs in mammalian cells. These results indicate that prion-like polymerization is a conserved signal transduction mechanism in innate immunity and inflammation.

Original languageEnglish (US)
Pages (from-to)1207-1222
Number of pages16
JournalCell
Volume156
Issue number6
DOIs
StatePublished - Mar 13 2014

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Inflammasomes
Signal transduction
Prions
Polymerization
Antiviral Agents
Signal Transduction
Chemical activation
Yeast
Yeasts
Cells
Cell signaling
Caspase 1
Functional polymers
Pathogens
Ports and harbors
Innate Immunity
Polymers
Inflammation
Mutation
Fibers

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Prion-like polymerization underlies signal transduction in antiviral immune defense and inflammasome activation. / Cai, Xin; Chen, Jueqi; Xu, Hui; Liu, Siqi; Jiang, Qiu Xing; Halfmann, Randal; Chen, Zhijian J.

In: Cell, Vol. 156, No. 6, 13.03.2014, p. 1207-1222.

Research output: Contribution to journalArticle

Cai, Xin ; Chen, Jueqi ; Xu, Hui ; Liu, Siqi ; Jiang, Qiu Xing ; Halfmann, Randal ; Chen, Zhijian J. / Prion-like polymerization underlies signal transduction in antiviral immune defense and inflammasome activation. In: Cell. 2014 ; Vol. 156, No. 6. pp. 1207-1222.
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