Prion-like polymerization underlies signal transduction in antiviral immune defense and inflammasome activation.
Prion-like polymerization underlies signal transduction in antiviral immune defense and inflammasome activation.
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朊病毒样聚合是抗病毒免疫防御和炎症小体激活中信号转导的基础。
DOI：
10.1016/j.cell.2014.01.063
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发表时间：
2014-03-13
期刊：
影响因子：
64.5
通讯作者：
Chen ZJ
中科院分区：
文献类型：
--
作者：
Cai X;Chen J;Xu H;Liu S;Jiang QX;Halfmann R;Chen ZJ
病原体和细胞危险信号激活诸如RIG-I和NLRP 3的传感器，以通过各自的衔接蛋白MAVS和ASC产生稳健的免疫和炎症应答，所述衔接蛋白MAVS和ASC分别具有必需的N-末端CARD和PYRIN结构域。在这里，我们表明，CARD和PYRIN作为真正的朊病毒在酵母中的功能和它们的朊病毒的形式是由它们各自的上游激活剂诱导。同样，酵母朊病毒结构域可以在哺乳动物细胞信号传导中功能性地取代CARD和PYRIN。MAVS和ASC中的突变破坏了它们在酵母中的朊病毒活性，也消除了它们在哺乳动物细胞中的信号传递能力。此外，重组PYRIN的纤维可以将ASC转化为能够激活半胱天冬酶-1的功能性聚合物。值得注意的是，保守的真菌NOD样受体和朊病毒对可以在哺乳动物细胞中功能性地重建NLRP 3和ASC PYRIN的信号传导。这些结果表明朊病毒样聚合是先天免疫和炎症中保守的信号转导机制。
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 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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影响因子：
16
作者：
Martinon, F;Burns, K;Tschopp, J
通讯作者：
Tschopp, J
影响因子：
64.5
作者：
Li J;McQuade T;Siemer AB;Napetschnig J;Moriwaki K;Hsiao YS;Damko E;Moquin D;Walz T;McDermott A;Chan FK;Wu H
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影响因子：
32.4
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Jiang X;Kinch LN;Brautigam CA;Chen X;Du F;Grishin NV;Chen ZJ
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Chen ZJ
影响因子：
64.5
作者：
Park, Hyun Ho;Logette, Emmanuelle;Wu, Hao
通讯作者：
Wu, Hao
影响因子：
32.4
作者：
Agostini, L;Martinon, F;Tschopp, J
通讯作者：
Tschopp, J