RACK1 Mediates NLRP3 Inflammasome Activation by Promoting NLRP3 Active Conformation and Inflammasome Assembly.
RACK1 Mediates NLRP3 Inflammasome Activation by Promoting NLRP3 Active Conformation and Inflammasome Assembly.
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RACK1通过促进NLRP3活性构象和炎性小体组装介导NLRP3炎性小体激活。
DOI：
10.1016/j.celrep.2020.108405
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发表时间：
2020-11-17
期刊：
影响因子：
8.8
通讯作者：
He Y
中科院分区：
文献类型：
--
作者：
Duan Y;Zhang L;Angosto-Bazarra D;Pelegrín P;Núñez G;He Y
NLRP3炎症体是先天免疫系统的重要组成部分，在微生物感染和细胞损伤时诱导Caspase-1激活和IL-1β成熟。然而，NLRP3炎症体的异常激活参与了几种炎症性疾病的发病，包括低温比林相关的周期性综合征、阿尔茨海默病、2型糖尿病和动脉粥样硬化。在这里，我们确定活化蛋白C激酶1的受体(RACK1)是巨噬细胞中NLRP3复合体的一个组成部分。RACK1与NLRP3和NEK7相互作用，但不与ASC相互作用。抑制RACK1的表达会抑制Caspase-1的激活和IL-1β的释放，而不是NLRP4或AIM2的激活刺激。这种RACK1功能不依赖于其核糖体结合活性。在机制上，RACK1通过激活刺激和随后的炎性小体组装促进NLRP3的活性构象。这些结果表明，RACK1是NLRP3炎性小体激活的关键介质。NLRP3炎症体是先天免疫系统的重要组成部分。Duan et al.研究表明，活化蛋白C激酶1受体(RACK1)通过促进NLRP3的活性构象和炎症体的组装来介导NLRP3炎症体的激活，从而确立RACK1是NLRP3炎症体的重要调节因子。
The NLRP3 inflammasome, a critical component of the innate immune system, induces caspase-1 activation and interleukin (IL)-1β maturation in response to microbial infection and cellular damage. However, aberrant activation of the NLRP3 inflammasome contributes to the pathogenesis of several inflammatory disorders, including cryopyrin-associated periodic syndromes, Alzheimer’s disease, type 2 diabetes, and atherosclerosis. Here, we identify the receptor for activated protein C kinase 1 (RACK1) as a component of the NLRP3 complexes in macrophages. RACK1 interacts with NLRP3 and NEK7 but not ASC. Suppression of RACK1 expression abrogates caspase-1 activation and IL-1β release in response to NLRP3- but not NLRC4- or AIM2-activating stimuli. This RACK1 function is independent of its ribosomal binding activity. Mechanistically, RACK1 promotes the active conformation of NLRP3 induced by activating stimuli and subsequent inflammasome assembly. These results demonstrate that RACK1 is a critical mediator for NLRP3 inflammasome activation. The NLRP3 inflammasome is a critical component of the innate immune system. Duan et al. show that the receptor for activated protein C kinase 1 (RACK1) mediates NLRP3 inflammasome activation by promoting NLRP3 active conformation and inflammasome assembly, thereby establishing RACK1 as an important regulator of the NLRP3 inflammasome.
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影响因子：
64.8
作者：
Cheng, Zhenyu;Li, Jian-Feng;Niu, Yajie;Zhang, Xue-Cheng;Woody, Owen Z.;Xiong, Yan;Djonovic, Slavica;Millet, Yves;Bush, Jenifer;McConkey, Brendan J.;Sheen, Jen;Ausubel, Frederick M.
通讯作者：
Ausubel, Frederick M.
影响因子：
16
作者：
Martinon, F;Burns, K;Tschopp, J
通讯作者：
Tschopp, J
DOI：
10.1073/pnas.0611496104
发表时间：
2007-05-08
影响因子：
11.1
作者：
Duncan, Joseph A.;Bergstralht, Daniel T.;Ting, Jenny Pan-Yun
通讯作者：
Ting, Jenny Pan-Yun
DOI：
10.1007/978-1-4939-3566-6_10
发表时间：
2016-01-01
期刊：
NLR PROTEINS: METHODS AND PROTOCOLS
影响因子：
--
作者：
Martin-Sanchez, Fatima;Compan, Vincent;Pelegrin, Pablo
通讯作者：
Pelegrin, Pablo
影响因子：
8
作者：
Mamidipudi, V.;Cartwright, C. A.
通讯作者：
Cartwright, C. A.