Non-decameric NLRP3 forms an MTOC-independent inflammasome
Bibliographic record
Abstract
Summary NLRP3 is an inflammasome-forming protein that plays a key role in conditions ranging from infections to Alzheimer’s disease. NLRP3 is activated by many potassium (K + )-dependent or - independent stimuli related to pathogens or sterile insults. Molecularly, human NLRP3 assembles into a decameric ‘cage’ and its interaction with both the trans-Golgi network (TGN) and the microtubule organization centre (MTOC) has been proposed as critical for NLRP3 activation. However, the relative mechanistic requirement for K + -dependent versus - independent stimuli is unclear. Using spatially and dynamically high-resolution microscopy in human macrophages, we found that K + -dependent NLRP3 stimulation triggers two distinct activation pathways: ( i ) the decameric cage-dependent pathway, which was also exclusively required for the K + -independent stimulus, imiquimod; and ( ii ) a cage- and TGN/MTOC-independent pathway that was fully functional in an NLRP3 protein engineered to form monomers and unable to interact with membrane lipids. Collectively, our results delineate two parallel yet biologically distinct NLRP3 activation pathways.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".