PtdIns4P on dispersed trans-Golgi network mediates NLRP3 inflammasome activation.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30487600.
- Also identified by DOI 10.1038/s41586-018-0761-3 and PMC identifier 9402428.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Inflammasomes
- NLR Family, Pyrin Domain-Containing 3 Protein
- Phosphatidylinositol Phosphates
- trans-Golgi Network