CLIC-dependent internalization of caveolin-1 to lysosomal vacuoles in response to osmotic regulation
Bibliographic record
Abstract
Abstract Originally thought to be a major endocytic portal, caveolae are now considered to function as a membrane buffer, whereby caveolae flattening protects the plasma membrane from rupture under mechanical stress, such as hypotonic shock. However, the fate of the caveolae coat protein caveolin-1 in response to hypotonic shock is not known. Here, we show that extended hypotonic shock induces ubiquitin-independent, CLIC-dependent endocytosis of caveolin-1 to large, intracellular, CD44-positive, pH-neutral lysosomal vacuoles negative for multivesicular body markers. Caveolin-1 recycles from these vacuoles to the plasma membrane upon return to isotonic conditions. Caveolin-1 internalizes not in response to initial cell expansion upon hypotonic shock but rather subsequent reduction of cell volume, and also in low-tension cells grown on reduced stiffness hydrogels. Upon hypertonic shock, caveolin-1 internalization occurs selectively in PC3 cells, lacking cavin-1, required for caveolae formation, and is inhibited upon cavin-1 reintroduction. CLIC endocytosis of non-caveolar caveolin-1 to neutral pH lysosomal vacuoles in response to osmotic regulation defines a novel recycling pathway enabling caveolae membrane buffering.
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How this classification was reachedexpand
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 | 0.001 | 0.001 |
| 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 | 0.001 | 0.001 |
| Research integrity | 0.001 | 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".