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PtdIns4P on dispersed trans-Golgi network mediates NLRP3 inflammasome activation

Author

Listed:
  • Jueqi Chen

    (University of Texas Southwestern Medical Center)

  • Zhijian J. Chen

    (University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center)

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.

Suggested Citation

  • Jueqi Chen & Zhijian J. Chen, 2018. "PtdIns4P on dispersed trans-Golgi network mediates NLRP3 inflammasome activation," Nature, Nature, vol. 564(7734), pages 71-76, December.
    • Handle: RePEc:nat:nature:v:564:y:2018:i:7734:d:10.1038_s41586-018-0761-3
    DOI: 10.1038/s41586-018-0761-3
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    Cited by:

    1. Zhi Feng & Shengnan Liu & Ming Su & Chunyu Song & Chenyu Lin & Fangying Zhao & Yang Li & Xianyan Zeng & Yong Zhu & Yu Hou & Chunguang Ren & Huan Zhang & Ping Yi & Yong Ji & Chao Wang & Hongtao Li & Mi, 2024. "TANGO6 regulates cell proliferation via COPI vesicle-mediated RPB2 nuclear entry," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Shouya Feng & Daniel Enosi Tuipulotu & Abhimanu Pandey & Weidong Jing & Cheng Shen & Chinh Ngo & Melkamu B. Tessema & Fei-Ju Li & Daniel Fox & Anukriti Mathur & Anyang Zhao & Runli Wang & Klaus Pfeffe, 2022. "Pathogen-selective killing by guanylate-binding proteins as a molecular mechanism leading to inflammasome signaling," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    3. Kelvin Ka Lok Wu & KeKao Long & Huige Lin & Parco Ming Fai Siu & Ruby Lai Chong Hoo & Dewei Ye & Aimin Xu & Kenneth King Yip Cheng, 2021. "The APPL1-Rab5 axis restricts NLRP3 inflammasome activation through early endosomal-dependent mitophagy in macrophages," Nature Communications, Nature, vol. 12(1), pages 1-17, December.

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