ER‐plasma membrane contact sites regulate sterol import in yeast
Bibliographic record
Abstract
Sterols must be distributed from their site of synthesis or point of import to other cellular membranes. The high, bidirectional flux of sterol between the ER and plasma membrane (PM), ~100,000 molecules/second, occurs by non‐vesicular mechanisms involving sterol transport proteins (STPs) that may localize to ER‐PM contact sites. In wild‐type yeast cells ~48% of the PM is closely associated with ER. To test whether this association plays a role in sterol transport, we created a yeast strain, Δ‐s‐tether (based on Δtether (Manford et al. (2012) Dev Cell 23:1129)), where ER‐PM contacts were largely absent. Electron microscopy of thin sections indicated that more than a third of the Δ‐s‐tether cells examined had no detectable contacts, and that on average only 1.7% of the PM was contacted by ER. We found that whereas Δ‐s‐tether cells display high levels of PM phosphatidylinositol‐4‐phosphate and choline‐dependent growth, consistent with lack of ER‐PM contacts, the rate at which newly synthesized ergosterol exchanges with the PM was surprisingly unaffected. However, transport of exogenously supplied sterol to the ER was slowed dramatically, an effect that could be reversed by growing the cells in choline or by over‐expressing an artificial ER‐PM tethering molecule. Our results suggest that ER‐PM contact sites control a critical step in sterol import.
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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 | 0.001 |
| 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".