TY - JOUR
T1 - Prion-like polymerization in immunity and inflammation
AU - Cai, Xin
AU - Xu, Hui
AU - Chen, Zhijian J.
N1 - Funding Information:
Research in our laboratory is supported by grants from the National Institutes of Health (AI-93967), the Welch Foundation (I-1389), and the Cancer Research Prevention Institute of Texas (RP120718 and RP120718). Z.J.C. is a Howard Hughes Medical Institute (HHMI) Investigator.
Publisher Copyright:
© 2017 Cold Spring Harbor Laboratory Press; all rights reserved.
PY - 2017/4
Y1 - 2017/4
N2 - The innate immune system relies on receptors that sense common signs of infection to trigger a robust host-defense response. Receptors such as RIG-I and NLRP3 activate downstream adaptors mitochondrial antiviral signaling (MAVS) and apoptosis-associated speck-like protein (ASC), respectively, to propagate immune and inflammatory signaling. Recent studies have indicated that both MAVS and ASC form functional prion-like polymers to propagate immune signaling. Here, we summarize the biochemical, genetic, and structural studies that characterize the prion-like behavior of MAVS and ASC in their respective signaling pathways. We then discuss prion-like polymerization as an evolutionarily conserved mechanism of signal transduction in innate immunity in light of the similarity between the NLRP3-ASC, the NLRP3-ASC pathway in mammals, and the NWD2-HET-s pathway in fungi. We conclude by outlining the unique advantages to signaling through functional prions and potential future directions in the field.
AB - The innate immune system relies on receptors that sense common signs of infection to trigger a robust host-defense response. Receptors such as RIG-I and NLRP3 activate downstream adaptors mitochondrial antiviral signaling (MAVS) and apoptosis-associated speck-like protein (ASC), respectively, to propagate immune and inflammatory signaling. Recent studies have indicated that both MAVS and ASC form functional prion-like polymers to propagate immune signaling. Here, we summarize the biochemical, genetic, and structural studies that characterize the prion-like behavior of MAVS and ASC in their respective signaling pathways. We then discuss prion-like polymerization as an evolutionarily conserved mechanism of signal transduction in innate immunity in light of the similarity between the NLRP3-ASC, the NLRP3-ASC pathway in mammals, and the NWD2-HET-s pathway in fungi. We conclude by outlining the unique advantages to signaling through functional prions and potential future directions in the field.
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U2 - 10.1101/cshperspect.a023580
DO - 10.1101/cshperspect.a023580
M3 - Article
C2 - 27881448
AN - SCOPUS:85017230204
SN - 1943-0264
VL - 9
JO - Cold Spring Harbor perspectives in biology
JF - Cold Spring Harbor perspectives in biology
IS - 4
M1 - a023580
ER -