Role of membrane contact sites in PM ‐ ER sterol transport (606.7)
Bibliographic record
Abstract
Intracellular trafficking of sterols occurs largely by non‐vesicular processes that are poorly understood. Cytoplasmic sterol transport proteins (STPs) are presumed to ferry sterols between membranes and this may be enhanced in regions where the participating membranes are closely apposed (membrane contact sites or MCSs). The major sterol trafficking pathway in the yeast Saccharomyces cerevisiae involves direct transfer between the endoplasmic reticulum (ER) and plasma membrane (PM). Yeast STPs have not been identified, although the cytoplasmic protein Kes1/Osh4 has been implicated in the phosphoinositide‐driven cycling of ergosterol between the ER and TGN. We considered whether MCSs between the ER and PM might play a role in sterol transport between the two organelles. We tested this hypothesis by analyzing sterol traffic in Saccharomyces cerevisiae cells that were largely devoid of ER ‐ PM contact sites (∆tether cells). We used fluorescence microscopy to track the retrograde movement of exogenously supplied dehydroergosterol (DHE) from the PM to the ER and lipid droplets, and high performance liquid chromatography to quantify, in parallel, the transport‐coupled formation of DHE esters. We found that sterol transport from PM to ER is unaffected in ∆tether cells. We are currently generating strains based on ∆tether cells in which all residual ER‐PM MCSs are eliminated, and also testing whether vesicular pathways might play a redundant role in the absence of MCSs.
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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 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 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".