Oxysterol-binding-protein (OSBP)-related protein 4 binds25-hydroxycholesterol and interacts with vimentin intermediate filaments
Bibliographic record
Abstract
Oxysterol-binding protein (OSBP) is the prototypical member of a class of phospholipid and oxysterol-binding proteins that interacts with the Golgi apparatus and regulates lipid and cholesterol metabolism. As a result of recent sequencing efforts, eleven other OSBP-related proteins (ORPs) have been identified in humans. We have investigated the structure, oxysterol-binding activity, cellular localization and function of ORP4 (also designated OSBP2 or HLM), a homologue that shares the highest degree of similarity with OSBP. Two ORP4 cDNAs were identified: a full-length ORP4 containing a pleckstrin homology (PH) domain and an oxysterol-binding region (designated ORP4-L), and a splice variant in which the PH domain and part of the oxysterol-binding domain were deleted (designated ORP4-S). ORP4 mRNA and protein expression overlapped partially with OSBP and were restricted to brain, heart, muscle and kidney. Like OSBP, ORP4-L bound [3H]25-hydroxycholesterol with high affinity and specificity. In contrast, ORP4-S did not bind [3H]25-hydroxycholesterol or [3H]7-ketocholesterol. Immunofluorescence localization in stably transfected Chinese hamster ovary cells showed that ORP4-S co-localized with vimentin and caused the intermediate filament network to bundle or aggregate. ORP4-L displayed a diffuse staining pattern that did not overlap with vimentin except when the microtubule network was disrupted with nocodazole. Oxysterols had no effect on the localization of either ORP4. Cells overexpressing ORP4-S had a 40% reduction in the esterification of low-density-lipoprotein-derived cholesterol, demonstrating that ORP4 interaction with intermediate filaments inhibits an intracellular cholesterol-transport pathway mediated by vimentin. These studies elucidate a hitherto unknown relationship between OSBPs and the intermediate filament network that influences cholesterol transport.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".