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Cited by 692Inflammasome and immune disordersImmune Response and InflammationCalcium signaling and nucleotide metabolism

PtdIns4P on dispersed trans-Golgi network mediates NLRP3 inflammasome activation

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Chen, Jueqi, Chen, Zhijian J.·2018·Nature
DOI 10.1038/s41586-018-0761-3PMC PMC9402428
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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.

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Cited by

Sorted by citations

Authors
Chen, J., & Chen, Z. J.
Affiliations
  • The University of Texas Southwestern Medical Center (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
Chen, Zhijian J.
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2018-11-28
Volume
564
Issue
7734
Pages
71-76
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/s41586-018-0761-3
PMC
PMC9402428
OpenAlex
W2902713146
Cited by
692
References
2
Citations by year
2026: 79 · 2025: 84 · 2024: 118 · 2023: 109 · 2022: 90 · 2021: 80 · 2020: 84 · 2019: 48
FWCI
18.86
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
  • Howard Hughes Medical Institute
  • Welch Foundation
  • University of Texas Southwestern Medical Center
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
Keywords
NLRP3 inflammasome, phosphatidylinositol 4-phosphate, trans-Golgi network, inflammasome activation, polybasic region, membrane phospholipids
MeSH terms
NLR Family, Pyrin Domain-Containing 3 Protein, Amino Acid Sequence, Animals, Humans, Potassium, Protein Binding, Signal Transduction, Ion Transport, Phosphatidylinositol Phosphates, trans-Golgi Network, HEK293 Cells, Inflammasomes

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