Oleate activates PLD2 lipase and GEF activity by modulating membrane microdomain dynamics via S-acylation
Bibliographic record
Abstract
Phospholipase D2 (PLD2) plays critical roles in cellular signaling, membrane dynamics, and cancer progression. Oleate (OA) has been shown to activate PLD2 and promote triple-negative breast cancer (TNBC) cell migration, but the underlying molecular mechanisms remain poorly understood. Using confocal microscopy, lipid raft isolation, and S-acylation assays, we show that OA enhanced PLD2 S-acylation at Cys223 and Cys224, disrupting its lipid raft localization, and consequently increasing its colocalization with PIP 2 -enriched microdomains. Furthermore, we identified PLD2 as a guanine nucleotide exchange factor (GEF) for Cdc42, with its GEF activity regulated by OA-dependent S-acylation and lipid raft dynamics. Mutation of the S-acylation sites or disruption of lipid rafts abolished PLD2-mediated Cdc42 activation and filopodia-like cell protrusion formation. These findings reveal a novel regulatory mechanism by which OA modulates PLD2 activity through S-acylation and membrane microdomain reorganization, providing new insights into the regulation of PLD2 in cell migration and signaling.
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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 | 0.000 |
| 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 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".