PtdIns4P on dispersed trans-Golgi network mediates NLRP3 inflammasome activation.

Abstract:

: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.

journal_name

Nature

journal_title

Nature

authors

Chen J,Chen ZJ

doi

10.1038/s41586-018-0761-3

subject

Has Abstract

pub_date

2018-12-01 00:00:00

pages

71-76

issue

7734

eissn

0028-0836

issn

1476-4687

pii

10.1038/s41586-018-0761-3

journal_volume

564

pub_type

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