The ASC Speck and NLRP3 Inflammasome Function Are Spatially and Temporally Distinct
Although considered the ternary inflammasome structure, whether the singular, perinuclear NLRP3:ASC speck is synonymous with the NLRP3 inflammasome is unclear. Herein, we report that the NLRP3:ASC speck is not required for nigericin-induced inflammasome activation but facilitates and maximizes IL-1β...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.752482/full |
| _version_ | 1818402167407509504 |
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| author | Abhinit Nagar Tabassum Rahman Jonathan A. Harton |
| author_facet | Abhinit Nagar Tabassum Rahman Jonathan A. Harton |
| author_sort | Abhinit Nagar |
| collection | DOAJ |
| description | Although considered the ternary inflammasome structure, whether the singular, perinuclear NLRP3:ASC speck is synonymous with the NLRP3 inflammasome is unclear. Herein, we report that the NLRP3:ASC speck is not required for nigericin-induced inflammasome activation but facilitates and maximizes IL-1β processing. Furthermore, the NLRP3 agonists H2O2 and MSU elicited IL-1β maturation without inducing specks. Notably, caspase-1 activity is spatially distinct from the speck, occurring at multiple cytoplasmic sites. Additionally, caspase-1 activity negatively regulates speck frequency and speck size, while speck numbers and IL-1β processing are negatively correlated, cyclical and can be uncoupled by NLRP3 mutations or inhibiting microtubule polymerization. Finally, when specks are present, caspase-1 is likely activated after leaving the speck structure. Thus, the speck is not the NLRP3 inflammasome itself, but is instead a dynamic structure which may amplify the NLRP3 response to weak stimuli by facilitating the formation and release of small NLRP3:ASC complexes which in turn activate caspase-1. |
| first_indexed | 2024-12-14T08:04:03Z |
| format | Article |
| id | doaj.art-1356e10e7d1f414a932cae769d70cd60 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-14T08:04:03Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-1356e10e7d1f414a932cae769d70cd602022-12-21T23:10:15ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-10-011210.3389/fimmu.2021.752482752482The ASC Speck and NLRP3 Inflammasome Function Are Spatially and Temporally DistinctAbhinit NagarTabassum RahmanJonathan A. HartonAlthough considered the ternary inflammasome structure, whether the singular, perinuclear NLRP3:ASC speck is synonymous with the NLRP3 inflammasome is unclear. Herein, we report that the NLRP3:ASC speck is not required for nigericin-induced inflammasome activation but facilitates and maximizes IL-1β processing. Furthermore, the NLRP3 agonists H2O2 and MSU elicited IL-1β maturation without inducing specks. Notably, caspase-1 activity is spatially distinct from the speck, occurring at multiple cytoplasmic sites. Additionally, caspase-1 activity negatively regulates speck frequency and speck size, while speck numbers and IL-1β processing are negatively correlated, cyclical and can be uncoupled by NLRP3 mutations or inhibiting microtubule polymerization. Finally, when specks are present, caspase-1 is likely activated after leaving the speck structure. Thus, the speck is not the NLRP3 inflammasome itself, but is instead a dynamic structure which may amplify the NLRP3 response to weak stimuli by facilitating the formation and release of small NLRP3:ASC complexes which in turn activate caspase-1.https://www.frontiersin.org/articles/10.3389/fimmu.2021.752482/fullspeckNLRP3inflammasomecaspase-1colchicineIL-1β |
| spellingShingle | Abhinit Nagar Tabassum Rahman Jonathan A. Harton The ASC Speck and NLRP3 Inflammasome Function Are Spatially and Temporally Distinct Frontiers in Immunology speck NLRP3 inflammasome caspase-1 colchicine IL-1β |
| title | The ASC Speck and NLRP3 Inflammasome Function Are Spatially and Temporally Distinct |
| title_full | The ASC Speck and NLRP3 Inflammasome Function Are Spatially and Temporally Distinct |
| title_fullStr | The ASC Speck and NLRP3 Inflammasome Function Are Spatially and Temporally Distinct |
| title_full_unstemmed | The ASC Speck and NLRP3 Inflammasome Function Are Spatially and Temporally Distinct |
| title_short | The ASC Speck and NLRP3 Inflammasome Function Are Spatially and Temporally Distinct |
| title_sort | asc speck and nlrp3 inflammasome function are spatially and temporally distinct |
| topic | speck NLRP3 inflammasome caspase-1 colchicine IL-1β |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.752482/full |
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