Membrane curvature elastic stress triggers recruitment of PML-II onto the inner nuclear membrane
Bibliographic record
Abstract
Promyelocytic leukemia (PML) protein isoform II is a component of PML nuclear bodies (PML NBs) that also forms patches on nuclear lipid droplets (nLDs) and the inner nuclear membrane (INM). Here we tested whether different metabolic treatments that induce membrane curvature elastic stress (CES) in the INM, detected by recruitment of CTP:phosphocholine cytidylyltransferase α (CCTα) and a nuclear diacylglycerol (DAG) biosensor, are a precondition for PML-II membrane association. We found that treatment of U2OS cells with unsaturated 18-carbon fatty acids and DAG acyltransferase inhibitors caused the rapid formation of PML patches on the INM that coincided with DAG enrichment and the recruitment and stabilization of CCTα, all of which were reversed upon removal of the CES stimulus. PML patches were depleted of canonical PML NB-associated proteins, occurred at sites of lamin depletion, were specific for the PML-II isoform, and occurred in cells regardless of their capacity to assemble nLDs. Induction of INM curvature stress by knockout of the terminal enzymes of the CDP-choline pathway or lipid activators of CCTα also promoted PML patches as well as stabilization of CCTα on the INM. We conclude that CES in the INM promotes the reversible assembly of PML-II-dependent membrane-associated patches.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".