P2Y <sub>1</sub> receptor signaling is controlled by interaction with the PDZ scaffold NHERF-2
Bibliographic record
Abstract
P2Y(1) purinergic receptors (P2Y(1)Rs) mediate rises in intracellular Ca(2+) in response to ATP, but the duration and characteristics of this Ca(2+) response are known to vary markedly in distinct cell types. We screened the P2Y(1)R carboxyl terminus against a recently created proteomic array of PDZ (PSD-95/Drosophila Discs large/ZO-1 homology) domains and identified a previously unrecognized, specific interaction with the second PDZ domain of the scaffold NHERF-2 (Na(+)/H(+) exchanger regulatory factor type 2). Furthermore, we found that P2Y(1)R and NHERF-2 associate in cells, allowing NHERF-2-mediated tethering of P2Y(1)R to key downstream effectors such as phospholipase Cbeta. Finally, we found that coexpression of P2Y(1)R with NHERF-2 in glial cells prolongs P2Y(1)R-mediated Ca(2+) signaling, whereas disruption of the P2Y(1)R-NHERF-2 interaction by point mutations attenuates the duration of P2Y(1)R-mediated Ca(2+) responses. These findings reveal that NHERF-2 is a key regulator of the cellular activity of P2Y(1)R and may therefore determine cell-specific differences in P2Y(1)R-mediated 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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".