Regulation of PI4KIIα distribution between the Golgi and endosomal compartments
Bibliographic record
Abstract
Phosphatidylinositol 4‐kinases (PI4Ks) are essential for trafficking along the secretory and degradative routes. The importance of PI4K localization is underscored by the role of PI4KIIα, an enzyme localized to trans‐Golgi and endosomes, in EGF receptor degradation and Wnt signaling, and its suspected role in the late‐onset neurodegeneration. Although membrane association of PI4KIIα through a palmitoyl moiety is suggestive of its cycling between endosomes and Golgi, little is known about the regulation of PI4KIIα subcellular localization. Here we performed a proteomic screen of potential binding partners of PI4KIIα and identified a vesicular fusion protein VAMP‐3, that was confirmed by co‐immunoprecipitation. Expression of Tetanus toxin (TeNT), which specifically cleaves VAMP‐3, resulted in accumulation of PI4KIIα on endosomes. Conversely, overexpression of TeNT with the TeNT‐resistant VAMP‐3 mutant recovered the Golgi localization of PI4KIIα. We also found that PI4KIIα rapidly trafficked back to the Golgi within 2–3 min following photobleaching of the Golgi subpopulation, whereas the rate of its reappearance was significantly decreased in the presence of TeNT. Collectively, these data suggest that VAMP‐3 regulates PI4KIIα retrograde transport, uncovering new aspects of the role of PI4KIIα in human health and disease. Supported by the NICHD Intramural research program
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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 | 0.001 | 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".