Phosphorylation of yeast glycerol 3‐phosphate acyltransferase Gpt2 regulates the timing of TAG synthesis and lipid droplet morphology
Bibliographic record
Abstract
Glycerol‐3‐phosphate acyltransferases catalyze the acylation of glycerol‐3‐phosphate at the sn‐1 position yielding 1‐acyl glycerol‐3‐phosphate (lyso‐phosphatidic acid). This is the first and rate limiting reaction in de‐novo synthesis of phosphatidic acid (PA), the key intermediate for the formation of all glycerophospholipids and triacylglycerols. In all eukaryotic organisms glycerol‐3‐phosphate acyltransferases as well as acyltransferases catalyzing the subsequent acylation reaction converting lyso‐PA to PA occur in redundancy. This led to the hypothesis that isoenzymes are forming different PA pools which supply different pathways. In the model organism yeast Saccharomyces cerevisiae two glycerol‐3‐phosphate acyltransferases have been identified, Gpt2 (Gat1) and Sct1 (Gat2). Most recently we demonstrated the important role of Gpt2 (but not Sct1) in cells challenged by oleic acid as the only carbon source. Whereas growth in oleic acid containing medium induced massive lipid particle accumulation in wild‐type cells, cells lacking GPT2 failed to accumulate these storage compartments of triacylglycerols and other non‐polar lipids, exhibited a strong growth defect and cell viability was significantly reduced. We were intrigued by the fact that the intracellular distribution of Gpt2 and its phosphorylation status changed under these growth condition compared to growth on glucose containing medium. We have identified several phosphorylation sites in Gpt2 by mass spectrometry, which are localized to a serine rich region in the carboxy‐terminus of the protein. Serine to alanine or to aspartate mutations as well as deletion of the serine rich region containing these residues, were introduced in the yeast genome to investigate the role of phosphorylation in the regulation of Gpt2. Importantly, all phosphorylation mutants were able to support life of cells lacking Sct1, indicating these mutants are functional. We show that manipulations of Gpt2 phosphorylation status strongly and specifically affect TAG accumulation, but not metabolism of the most abundant glycerophospholipids during late log phase of growth. Importantly, alterations in the TAG content are accompanied by marked changes in lipid droplet morphology in the respective mutants. Altogether our results support a role for Gpt2 phosphorylation in regulating the timing of TAG synthesis and lipid droplet morphology. Support or Funding Information This work has been financially supported by the Natural Sciences and Engineering Research Council of Canada (to VZ and BS) and the Austrian Science Fund (FWF; Project P21251 to KA).
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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".