P3‐337: S‐palmitoylation targets BACE‐1 to lipid rafts
Bibliographic record
Abstract
Several studies have previously highlighted the importance of cholesterol-rich lipid raft membrane microdomains in the processing of amyloid precursor protein (APP) by β- and γ-secretases to release Alzheimer's disease-associated amyloid peptides (Aβ). Biochemical fractionation and antibody co-patching methods indicate that a significant fraction of the β-secretase BACE-1 is targeted to lipid rafts. However, the molecular determinants responsible for BACE-1 targeting to lipid rafts are still unknown. Radiolabeled palmitic acid labeling, biochemical lipid rafts-isolation, Western blot, antibody co-patching, immunocytochemistry Here, we show that BACE-1 undergoes post-translational S-palmitoylation at four cysteine residues within the transmembrane and cytosolic domains. Substitution of these 4 cysteines to alanines was sufficient to abolish BACE-1 S-palmitoylation and targeting to lipid raft domains. However, wild type and palmitoylation-defective BACE-1 appear to have similar subcellular distribution in stably transfected cell lines. We also identified a subset of DHHC-containing palmitoyl-transferases that were able to mediate BACE-1 S-palmitoylation. Our studies indicate that S-palmitoylation is required for BACE-1 targeting to lipid rafts. As S-palmitoylation is a reversible post-translational modification, DHHC-containing palmitoyl-transferase activities might mediate dynamic modulation of BACE-1 association to lipid rafts.
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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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".