Stabilization of Caveolin-1 by Cellular Cholesterol and Scavenger Receptor Class B Type I
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Bibliographic record
Abstract
Caveolae are 50-100 nm plasma membrane invaginations, which function in cell signaling, in transcytosis, and in regulating cellular cholesterol homeostasis. These subcompartments of the plasma membrane are characterized by the presence of caveolin proteins. Recent studies have indicated that caveolae may be involved in the regulation of cellular cholesterol efflux to high-density lipoproteins (HDL), as well as selective cholesteryl ester uptake mediated by scavenger receptor class B type I (SR-BI). In the present studies, we show that caveolin-1 expression in HEK-293T cells has no effect on SR-BI-mediated cellular cholesterol efflux to reconstituted HDL. However, SR-BI-mediated selective cholesteryl ester uptake is significantly inhibited by caveolin-1. Interestingly, we also found that SR-BI, but not CD36, can induce the dramatic stabilization of the caveolin-1 protein, independently of its transcriptional control. On the other hand, caveolin-1 has little effect on SR-BI stability, but clearly increases CD36 stability. Since SR-BI expression has been shown to increase cellular cholesterol levels, we next examined the effect of cholesterol itself on caveolin-1 stabilization and localization. When cells were loaded with cholesterol, we observed the dramatic stabilization of caveolin-1 with significant clustering of caveolin-1 at the cell surface. In addition, a palmitoylation-deficient caveolin-1 mutant was still responsive to cholesterol-induced stabilization, indicating that palmitoylation of caveolin-1 is not required for the cholesterol-induced stabilization of caveolin-1. These results suggest an important role for cholesterol and SR-BI in the regulation of caveolin functioning, especially in cell types such as endothelial cells and macrophages, which can be dramatically affected by changes in their cholesterol content during the development of atherosclerosis.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 it