PKR-dependent cytosolic cGAS foci are necessary for intracellular DNA sensing

被引：60

作者：

Hu, Siqi ^{[1
,2
]}

Sun, Hong ^{[1
,2
]}

Yin, Lijuan ^{[1
,2
]}

Li, Jian ^{[1
,2
]}

Mei, Shan ^{[1
,2
]}

Xu, Fengwen ^{[1
,2
]}

Wu, Chao ^{[3
,4
]}

Liu, Xiaoman ^{[1
,2
]}

Zhao, Fei ^{[1
,2
]}

Zhang, Di ^{[1
,2
]}

Huang, Yu ^{[1
,2
]}

Ren, Lili ^{[3
,4
]}

Cen, Shan ^{[5
]}

Wang, Jianwei ^{[3
,4
]}

Liang, Chen ^{[6
]}

Guo, Fei ^{[1
,2
]}

机构：

[1] Chinese Acad Med Sci & Peking Union Med Coll, Inst Pathogen Biol, NHC Key Lab Syst Biol Pathogens, Beijing 100730, Peoples R China

[2] Chinese Acad Med Sci & Peking Union Med Coll, Ctr AIDS Res, Beijing 100730, Peoples R China

[3] Chinese Acad Med Sci & Peking Union Med Coll, NHC Key Lab Syst Biol Pathogens, IPB Fondat Merieux, Inst Pathogen Biol, Beijing 100730, Peoples R China

[4] Chinese Acad Med Sci & Peking Union Med Coll, Christophe Merieux Lab, IPB Fondat Merieux, Inst Pathogen Biol, Beijing 100730, Peoples R China

[5] Chinese Acad Med Sci & Peking Union Med Coll, Inst Med Biotechnol, Beijing 100005, Peoples R China

[6] McGill Univ, AIDS Ctr, Lady Davis Inst, Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada

来源：

SCIENCE SIGNALING | 2019年 / 12卷 / 609期

基金：

中国国家自然科学基金; 加拿大健康研究院;

关键词：

CYCLIC GMP-AMP; PROTEIN-KINASE PKR; GTPASE-ACTIVATING PROTEIN; BINDING-PROTEIN; ENDOGENOUS; 2ND-MESSENGER; INNATE IMMUNITY; STRESS; RAS; RECOGNITION; GRANULES;

D O I：

10.1126/scisignal.aav7934

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Cyclic GMP-AMP synthase (cGAS) is a major sensor of cytosolic DNA from invading pathogens and damaged cellular organelles. Activation of cGAS promotes liquid-like phase separation and formation of membraneless cytoplasmic structures. Here, we found that cGAS bound G3BP1, a double-stranded nucleic acid helicase involved in the formation of stress granules. Loss of G3BP1 blocked subcellular cGAS condensation and suppressed the interferon response to intracellular DNA and DNA virus particles in cells. Furthermore, an RNA-dependent association with PKR promoted G3BP1 foci formation and cGAS-dependent interferon responses. Together, these results indicate that PKR promotes the formation of G3BP1-dependent, membraneless cytoplasmic structures necessary for the DNA-sensing function of cGAS in human cells. These data suggest that there is a previously unappreciated link between nucleic acid sensing pathways, which requires the formation of specialized subcellular structures.

引用

页数：13

共 75 条

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