S-acylation of NLRP3 provides a nigericin sensitive gating mechanism that controls access to the Golgi
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...
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eLife Sciences Publications Ltd
2024-09-01
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| Online Access: | https://elifesciences.org/articles/94302 |
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| author | Daniel M Williams Andrew A Peden |
| author_facet | Daniel M Williams Andrew A Peden |
| author_sort | Daniel M Williams |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-ce7e5b87b80a4c0e8825849fe27eea5f |
| institution | OA Journals |
| issn | 2050-084X |
| language | English |
| publishDate | 2024-09-01 |
| publisher | eLife Sciences Publications Ltd |
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| series | eLife |
| spelling | doaj-art-ce7e5b87b80a4c0e8825849fe27eea5f2025-08-20T01:56:01ZengeLife Sciences Publications LtdeLife2050-084X2024-09-011310.7554/eLife.94302S-acylation of NLRP3 provides a nigericin sensitive gating mechanism that controls access to the GolgiDaniel M Williams0https://orcid.org/0000-0001-8483-021XAndrew A Peden1https://orcid.org/0000-0003-0144-7712School of Bioscience, University of Sheffield, Sheffield, United KingdomSchool of Bioscience, University of Sheffield, Sheffield, United KingdomNLRP3 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.https://elifesciences.org/articles/94302inflammasomeslipidationGolgimembrane trafficking |
| spellingShingle | Daniel M Williams Andrew A Peden S-acylation of NLRP3 provides a nigericin sensitive gating mechanism that controls access to the Golgi eLife inflammasomes lipidation Golgi membrane trafficking |
| title | S-acylation of NLRP3 provides a nigericin sensitive gating mechanism that controls access to the Golgi |
| title_full | S-acylation of NLRP3 provides a nigericin sensitive gating mechanism that controls access to the Golgi |
| title_fullStr | S-acylation of NLRP3 provides a nigericin sensitive gating mechanism that controls access to the Golgi |
| title_full_unstemmed | S-acylation of NLRP3 provides a nigericin sensitive gating mechanism that controls access to the Golgi |
| title_short | S-acylation of NLRP3 provides a nigericin sensitive gating mechanism that controls access to the Golgi |
| title_sort | s acylation of nlrp3 provides a nigericin sensitive gating mechanism that controls access to the golgi |
| topic | inflammasomes lipidation Golgi membrane trafficking |
| url | https://elifesciences.org/articles/94302 |
| work_keys_str_mv | AT danielmwilliams sacylationofnlrp3providesanigericinsensitivegatingmechanismthatcontrolsaccesstothegolgi AT andrewapeden sacylationofnlrp3providesanigericinsensitivegatingmechanismthatcontrolsaccesstothegolgi |