Novel Interactions of Yeast Glycerol‐3‐Phosphate Acyltransferases
Bibliographic record
Abstract
Glycerol‐3‐phosphate acyltransferases (GPATs) catalyze the first committed and rate limiting step in the de novo synthesis of glycerophospholipids and neutral triacylglycerols. GPATs transfer an acyl group from acyl‐coenzyme A to the sn‐1 position of glycerol‐3‐phosphate to produce 1‐acyl glycerol‐3‐phosphate (lysophosphatidic acid). Lysophosphatidic acid can then be further acylated by a second acyltransferase to produce phosphatidic acid, a signalling lipid and key intermediate in lipid biosynthesis. In the model organism yeast Saccharomyces cerevisiae two GPATs, Gpt2 and Sct1, have been identified. Both are integral membrane proteins located to the endoplasmic reticulum (ER), differentially enriched in ER domains. Interestingly, we have shown that Gpt2 (but not Sct1) is responsible for channeling oleate (C18:1) into triacylglycerol that is eventually stored in lipid droplets. Furthermore, our studies on oleate metabolism unveiled novel ER structures that surround lipid droplets and are differentially enriched in Gpt2 while devoid of Sct1. In addition, we also uncovered a dynamic post‐translational regulation of Gpt2 and Sct1 through phosphorylation that responds to growth phase, carbon source and cellular GPAT imbalance. The aim of this work was to understand how GPAT interactions with other proteins contribute to their spatial distribution in the ER and to lipid synthesis partitioning. In order to identify potential protein interactors, Gpt2 and Sct1 were overproduced in cells deleted for endogenous GPATs and then isolated from lysates and microsomes using co‐immuno‐affinity and Ni‐NTA affinity chromatography purification techniques. Potential interactors co‐purifying with Gpt2 or Sct1 were identified through liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). Our results suggest that Gpt2 and Sct1 differentially associate with ER sites where inter‐organelle transport of lipids occurs. Of importance are the contact sites between ER‐mitochondria, ER‐lipid droplets and the nuclear‐vacuolar junction. Support or Funding Information This work was supported by an operating grant from the Natural Sciences and Engineering Research Council of Canada to VZ.
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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) | 0.001 | 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".