PtdIns4P on dispersed trans-Golgi network mediates NLRP3 inflammasome activation

Nature. 2018 Dec;564(7734):71-76. doi: 10.1038/s41586-018-0761-3. Epub 2018 Nov 28.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • HEK293 Cells
  • Humans
  • Inflammasomes / metabolism*
  • Ion Transport
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Phosphatidylinositol Phosphates / metabolism*
  • Potassium / metabolism
  • Protein Binding
  • Signal Transduction
  • trans-Golgi Network / metabolism*


  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • Phosphatidylinositol Phosphates
  • phosphatidylinositol 4-phosphate
  • Potassium