Abstract 1624 Regulation of phosphatidylcholine synthesis at the inner nuclear membrane and nuclear lipid droplets
Bibliographic record
Abstract
The inner nuclear membrane (INM) can receive lipids by lateral diffusion from the outer nuclear membrane and endoplasmic reticulum (ER) at nuclear pores contacts.However, the INM and nucleoplasm also harbour phospholipid and triacylglycerol (TAG) biosynthetic enzymes, and assemble nuclear lipid droplets (nLDs) and lipid-associated PML structures (LAPS) from excess fatty acids.The CDP-choline pathway for synthesis of phosphatidylcholine, a major component of membranes and the surface monolayer of lipid droplets, terminates in the ER and Golgi apparatus but is regulated in the nucleus by the ratelimiting enzyme CTP:phosphocholine cytidylyltransferase α (CCTα).Changes in demand for phosphatidylcholine (PC) are relayed to CCTα via alterations in the structure and lipid composition of the INM and nLDs.An amphipathic helix in CCTα senses these compositional variations in the INM and nLDs and mediates enzyme translocation and activation.We treated hepatoma and osteosarcoma cells with oleate to identify factors that control the temporal association of CCTα with the INM and nLDs.The acute treatment of cells with oleate promoted translocation to the INM in 15-30 min and was accompanied by dephosphorylation of the serine-rich C-terminal P-domain.Oleate exposure for <2-3 h promoted the formation of nLDs and LAPS that gradually accumulated CCTα on their surface.The association of CCTα with nLDs and LAPS was proportional to available surface area and prevented by bulk phosphorylation of the P-domain.Blocking TAG synthesis with diacylglycerol acyltransferase inhibitors (iDGAT) trapped CCTα, Lipin1 and PML on the INM by a mechanism that was dependent on fatty acids but not DAG.Trapping CCTα on the INM of DGATi-treated cells increased its expression by inhibition of proteasomal degradation.The CCTα activators oleoyl alcohol and farnesol recapitulated these effect of oleate and DGATi.In contrast, CCTα on nLDs was not shielded against proteolytic degradation.We conclude that oleate provides the initial stimulus for CCTα association with the INM, followed by a shift to nLDs and LAPS as the surface monolayer increases due to TAG synthesis.Prolonging the acute phase of CCTα activation on the INM enhanced enzyme expression by blocking proteolytic degradation.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.004 | 0.003 |
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 source (direct Gemma or distilled Codex), 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".