CTP:phosphocholine cytidylyltransferase alpha regulates nLD biogenesis in Caco2 cells
Bibliographic record
Abstract
Recent investigations reveal that nuclear lipid droplets (nLDs) stimulate lipid metabolic enzymes in response to excess fatty acid loading of cells. For example, in oleate‐treated hepatocytes the rate‐limiting enzyme in the CDP‐choline pathway, CTP:phosphocholine cytidylyltransferase alpha (CCT alpha), is recruited to the surface of nLDs and stimulates the synthesis of phosphatidylcholine (PC). Hepatocyte nLDs derive from ApoB‐free LDs in the lumen of the endoplasmic reticulum that migrate into the nucleoplasm through type I nucleoplasmic reticulum invaginations of the inner nuclear membrane (INM). Once formed inside the nucleus, nLDs recruit proteins CCT alpha, Lipin1 and promyelocytic leukemia (PML) to their surfaces. Endothelial cells of the colon also express ApoB lipoproteins for chylomicron assembly and secretion, so we hypothesized that these cells might also form nLDs in response to excess lipid loading. Indeed, using immunofluorescence confocal microscopy we found that oleate‐treated Caco2 cells formed between 5 to 10 nLDs per cell that recruited both CCT alpha and PML to their surface. CRISPR/Cas9‐mediated CCT alpha knockout Caco2 (CCT alphaKO) cells had significantly fewer but larger cLDs and nLDs compared to wild‐type cells. The percentage of PML‐positive nLDs increased in CCT alphaKO cells, suggesting that CCT alpha and PML compete for access to the nLD surface following oleate treatment. To determine if phosphorylation of CCT alpha regulates translocation to nLDs, phospho‐mimetic and phospho‐null S315/S319 and Y359/S362 mutants were expressed in CCT alphaKO cells and localization to nLDs was measured. In vitro phosphorylation assays of recombinant, dephosphorylated CCT alpha indicated that AMP‐dependent kinase phosphorylated CCT alpha S319, which could be involved in regulating CCT alpha activity on nLDs. In summary, we have demonstrated that oleate treatment induces nLD biogenesis in Caco2 cells and that CCT alpha activity regulates the biogenesis of both nLDs and cLDs.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".