AI Article Synopsis
- NLRP3 is an inflammasome receptor that gets activated by signals that disturb cell balance and is recruited to the trans-Golgi network (TGN) through electrostatic interactions with lipids.
- A conserved cysteine residue (Cys-130) is shown to be critical for NLRP3's membrane association via a dynamic S-acylation cycle, which helps retain NLRP3 at the Golgi.
- Disruption in Golgi function from nigericin treatment leads to NLRP3 being trapped at the Golgi due to reduced de-acylation, linking Golgi homeostasis directly to NLRP3's activity through its acylation state.
Article Abstract
NLRP3 is an inflammasome seeding pattern recognition receptor activated in response to multiple danger signals which perturb intracellular homeostasis. Electrostatic interactions between the NLRP3 polybasic (PB) region and negatively charged lipids on the trans-Golgi network (TGN) have been proposed to recruit NLRP3 to the TGN. In this study, we demonstrate that membrane association of NLRP3 is critically dependant on S-acylation of a highly conserved cysteine residue (Cys-130), which traps NLRP3 in a dynamic S-acylation cycle at the Golgi, and a series of hydrophobic residues preceding Cys-130 which act in conjunction with the PB region to facilitate Cys-130 dependent Golgi enrichment. Due to segregation from Golgi localised thioesterase enzymes caused by a nigericin induced breakdown in Golgi organisation and function, NLRP3 becomes immobilised on the Golgi through reduced de-acylation of its Cys-130 lipid anchor, suggesting that disruptions in Golgi homeostasis are conveyed to NLRP3 through its acylation state. Thus, our work defines a nigericin sensitive S-acylation cycle that gates access of NLRP3 to the Golgi.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11392533 | PMC |
| http://dx.doi.org/10.7554/eLife.94302 | DOI Listing |
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Article Synopsis
- NLRP3 is an inflammasome receptor that gets activated by signals that disturb cell balance and is recruited to the trans-Golgi network (TGN) through electrostatic interactions with lipids.
- A conserved cysteine residue (Cys-130) is shown to be critical for NLRP3's membrane association via a dynamic S-acylation cycle, which helps retain NLRP3 at the Golgi.
- Disruption in Golgi function from nigericin treatment leads to NLRP3 being trapped at the Golgi due to reduced de-acylation, linking Golgi homeostasis directly to NLRP3's activity through its acylation state.
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