The ASC Speck and NLRP3 Inflammasome Function Are Spatially and Temporally Distinct.
The ASC Speck and NLRP3 Inflammasome Function Are Spatially and Temporally Distinct.
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DOI：
10.3389/fimmu.2021.752482
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发表时间：
2021
影响因子：
7.3
通讯作者：
Harton JA
中科院分区：
文献类型：
--
作者：
Nagar A;Rahman T;Harton JA
尽管考虑到三元炎性小体结构，但尚不清楚单个核周NLRP 3：ASC斑点是否与NLRP 3炎性小体同义。在此，我们报告NLRP 3：ASC斑点不是尼日利亚菌素诱导的炎性小体激活所必需的，但促进并最大化IL-1β加工。此外，NLRP 3激动剂H2 O2和MSU引起IL-1β成熟而不诱导斑点。值得注意的是，半胱天冬酶-1活性在空间上与斑点不同，发生在多个细胞质位点。此外，半胱天冬酶-1活性负调节斑点频率和斑点大小，而斑点数量和IL-1β加工呈负相关，呈周期性，并且可以通过NLRP 3突变或抑制微管聚合而解偶联。最后，当斑点存在时，caspase-1可能在离开斑点结构后被激活。因此，斑点不是NLRP 3炎性小体本身，而是一种动态结构，其可以通过促进小NLRP 3：ASC复合物的形成和释放来放大NLRP 3对弱刺激的响应，所述小NLRP 3：ASC复合物进而激活半胱天冬酶-1。
Although considered the ternary inflammasome structure, whether the singular, perinuclear NLRP3:ASC speck is synonymous with the NLRP3 inflammasome is unclear. Herein, we report that the NLRP3:ASC speck is not required for nigericin-induced inflammasome activation but facilitates and maximizes IL-1β processing. Furthermore, the NLRP3 agonists H2O2 and MSU elicited IL-1β maturation without inducing specks. Notably, caspase-1 activity is spatially distinct from the speck, occurring at multiple cytoplasmic sites. Additionally, caspase-1 activity negatively regulates speck frequency and speck size, while speck numbers and IL-1β processing are negatively correlated, cyclical and can be uncoupled by NLRP3 mutations or inhibiting microtubule polymerization. Finally, when specks are present, caspase-1 is likely activated after leaving the speck structure. Thus, the speck is not the NLRP3 inflammasome itself, but is instead a dynamic structure which may amplify the NLRP3 response to weak stimuli by facilitating the formation and release of small NLRP3:ASC complexes which in turn activate caspase-1.
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影响因子：
64.5
作者：
Kagan JC
通讯作者：
Kagan JC
DOI：
10.4049/jimmunol.0802367
发表时间：
2009-03-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Bryan NB;Dorfleutner A;Rojanasakul Y;Stehlik C
通讯作者：
Stehlik C
影响因子：
8.7
作者：
Elliott EI;Sutterwala FS
通讯作者：
Sutterwala FS
影响因子：
4.8
作者：
Atianand, Maninjay K.;Harton, Jonathan A.
通讯作者：
Harton, Jonathan A.
影响因子：
30.5
作者：
Baroja-Mazo, Alberto;Martin-Sanchez, Fatima;Pelegrin, Pablo
通讯作者：
Pelegrin, Pablo