Prion-like Polymerization Underlies Signal Transduction in Antiviral Immune Defense and Inflammasome Activation

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2014 Mar 18

PMID 24630723

Citations 321

Authors

Xin Cai

Jueqi Chen

Hui Xu

Siqi Liu

Qiu-Xing Jiang

Randal Halfmann

Zhijian J Chen

Affiliations

Soon will be listed here.

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.

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