Molecular regulation of lysophosphatidic acid receptor endocytosis and desensitization
Bibliographic record
Abstract
Lysophosphatidic Acid (LPA) is a major constituent of serum and is involved in a variety of physiological and pathophysiological processes. LPA signals via the G‐protein coupled receptors (GPCRs), LPA 1–3 , but the mechanisms regulating LPA receptor desensitization and endocytosis are unknown. GPCRs can internalize via clathrin‐dependent mechanisms and/or lipid rafts and caveolae. We show that Flag‐LPA 1 and ‐LPA 2 receptors do not partition into lipid rafts of LPA treated human embryonic kidney (HEK) 293 cells suggesting that LPA 1 and LPA 2 do not internalize via caveolae. Surprisingly, the expression of dynamin‐1 and ‐2 mutant proteins does not affect receptor internalization. We also examined whether RalA and phospholipase Ds, shown to regulate the endocytosis of certain GPCRs, contribute to LPA receptor endocytosis. Although these proteins interact constitutively and co‐localize with both LPA 1 and LPA 2 in endocytic vesicles, expression of wild‐type or mutant forms of these proteins did not affect receptor internalization. Finally, we observed that the expression of GRK2 and βarrestins mediated the desensitization of LPA 1 and LPA 2 by attenuating LPA induced inositol phosphate production. In summary, RalA and PLDs may not mediate LPA 1 or LPA 2 endocytosis, but may act as scaffolding proteins linking the receptors to other signaling pathways. This study is funded by NSERC grant awarded to Dr. M Bhattacharya
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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) | 0.001 | 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".