Right place, right time: localisation and assembly of the NLRP3 inflammasome.
Right place, right time: localisation and assembly of the NLRP3 inflammasome.
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DOI：
10.12688/f1000research.18557.1
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发表时间：
2019-01-01
期刊：
影响因子：
--
通讯作者：
Anand, Paras K
中科院分区：
文献类型：
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作者：
Hamilton, Claire;Anand, Paras K
NLRP3 炎症小体是一种多聚蛋白复合物，可裂解 caspase-1 和促炎细胞因子白细胞介素 1β (IL-1beta) 和 IL-18。 NLRP3 炎症小体信号传导失调与多种慢性炎症和自身免疫性疾病有关；因此，了解 NLRP3 炎症小体的激活机制至关重要。过去几年的研究表明，不同的细胞内细胞器在 NLRP3 炎症小体的定位和组装中发挥着重要作用。然而，存在相互矛盾的报道。在激活之前，NLRP3 已被证明驻留在内质网 (ER) 和细胞质中，尽管不同的报告表明，NLRP3 炎症小体在激活后会在细胞质、线粒体和线粒体相关的 ER 膜中组装。最后，最近的研究表明，NLRP3 可能位于高尔基体上或附近，并且该细胞器释放的介质可能有助于炎症小体的组装。因此，NLRP3 可以策略性地放置在这些亚细胞区室上或附近，以感知源自这些细胞器的危险信号，并使用该区室作为组装复合物的支架。了解 NLRP3 炎性体组装发生的地点和时间可能有助于确定治疗 NLRP3 相关疾病的潜在靶标。
The NLRP3 inflammasome is a multimeric protein complex that cleaves caspase-1 and the pro-inflammatory cytokines interleukin 1 beta (IL-1beta) and IL-18. Dysregulated NLRP3 inflammasome signalling is linked to several chronic inflammatory and autoimmune conditions; thus, understanding the activation mechanisms of the NLRP3 inflammasome is essential. Studies over the past few years have implicated vital roles for distinct intracellular organelles in both the localisation and assembly of the NLRP3 inflammasome. However, conflicting reports exist. Prior to its activation, NLRP3 has been shown to be resident in the endoplasmic reticulum (ER) and cytosol, although, upon activation, the NLRP3 inflammasome has been shown to assemble in the cytosol, mitochondria, and mitochondria-associated ER membranes by different reports. Finally, very recent work has suggested that NLRP3 may be localised on or adjacent to the Golgi apparatus and that release of mediators from this organelle may contribute to inflammasome assembly. Therefore, NLRP3 may be strategically placed on or in close proximity to these subcellular compartments to both sense danger signals originating from these organelles and use the compartment as a scaffold to assemble the complex. Understanding where and when NLRP3 inflammasome assembly occurs may help identify potential targets for treatment of NLRP3-related disorders.