PtdIns4P on dispersed trans-Golgi network mediates NLRP3 inflammasome activation

被引：533

作者：

Chen, Jueqi ^{[1
]}

Chen, Zhijian J. ^{[1
,2
]}

机构：

[1] Univ Texas Southwestern Med Ctr Dallas, Dept Biol Mol, Dallas, TX 75390 USA

[2] Univ Texas Southwestern Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA

来源：

NATURE | 2018年 / 564卷 / 7734期

关键词：

K+ EFFLUX; PHOSPHOINOSITIDES; RECRUITMENT; MECHANISM; PROTEINS;

D O I：

10.1038/s41586-018-0761-3

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The NLRP3 inflammasome, which has been linked to human inflammatory diseases, is activated by diverse stimuli. How these stimuli activate NLRP3 is unknown. Here we show that different NLRP3 stimuli lead to disassembly of the trans-Golgi network (TGN). NLRP3 is recruited to the dispersed TGN (dTGN) through ionic bonding between its conserved polybasic region and negatively charged phosphatidylinositol-4-phosphate (PtdIns4P) on the dTGN. The dTGN then serves as a scaffold for NLRP3 aggregation into multiple puncta, leading to polymerization of the adaptor protein ASC, thereby activating the downstream signalling cascade. Disruption of the interaction between NLRP3 and PtdIns4P on the dTGN blocked NLRP3 aggregation and downstream signalling. These results indicate that recruitment of NLRP3 to dTGN is an early and common cellular event that leads to NLRP3 aggregation and activation in response to diverse stimuli.

引用

页码：71 / +

页数：23

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