Abstract 77: Proprotein Convertase Subtilisin/kexin Type 9 (PCSK9) Targets the CD36 Receptor for Degradation
Bibliographic record
Abstract
The scavenger receptor CD36 is a membrane glycoprotein with broad ligand specificity that is highly expressed in metabolic tissues. Major functions of CD36 include the uptake of long chain fatty acids in fat tissue, heart and skeletal muscle and the uptake of oxidized lipoproteins in macrophages. Recent findings have also demonstrated that this protein regulates adipogenesis and adipocyte lipolysis. Thus, CD36 plays important roles in energy utilization from fatty acids and in lipoprotein and lipid homeostasis. However, dysfunction of CD36 has been linked to glucose intolerance, diabetes, atherosclerosis, arterial hypertension and cardiomyopathy. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted glycoprotein that regulates plasma low-density lipoprotein (LDL) cholesterol metabolism by promoting degradation of the hepatic LDL receptor. Here, we report that PCSK9 also induces the degradation of the CD36 receptor. Both cellular expression and secreted exogenous PCSK9 strongly downregulated the levels of CD36 protein in several cell lines. In addition, immunofluorescence analysis using the HepG2-hCD36 cell line demonstrated that the overexpression of PCSK9 decreases the levels of CD36 in parallel with a decrease in the uptake of oxidized LDL. Furthermore, treatment of 3T3-L1 adipocytes with purified soluble PCSK9 protein resulted in a decrease in CD36 protein expression at the cell surface and in the total cellular pool in a dose-dependent manner. Interestingly, we showed that CD36 degradation is modulated by PCSK9 in a proteasome- and lysosome-dependent manner. Co-immunoprecipitation assays in HEK293 cells confirmed CD36 ubiquitination in presence of PCSK9 and also revealed that PCSK9 associates in a complex with CD36. These results support a potential role for PCSK9 to impact the function of CD36 in lipid metabolism.
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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) | 0.000 | 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 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".