Sustained Gα <sub>s</sub> signaling mediated by vasopressin type 2 receptors is ligand dependent but endocytosis and β-arrestin independent
Bibliographic record
Abstract
The canonical model of G protein–coupled receptor (GPCR) signaling comprises G protein activation at the plasma membrane, followed by receptor phosphorylation and β-arrestin recruitment, which leads to receptor desensitization and endocytosis. However, the activation of some GPCRs results in sustained G protein signaling from intracellular compartments in a manner reportedly dependent on β-arrestin and receptor endocytosis. The vasopressin type 2 receptor (V 2 R) can be activated by two structurally similar hormones, arginine vasopressin and oxytocin, both of which stimulate the production of the second messenger cyclic adenosine monophosphate (cAMP). In this study, we showed that sustained V 2 R signaling and endosomal Gα s (stimulatory G protein alpha subunit) translocation could occur without β-arrestin–mediated receptor endocytosis and was primarily controlled by the residence time of the ligand on the receptor. β-Arrestin had opposing effects on sustained signaling: It facilitated receptor internalization into endosomes, where it activated Gα s , and promoted cAMP production from this compartment. However, β-arrestin–mediated receptor endocytosis also induced ligand dissociation due to the acidic endosomal environment, thereby limiting the signal. Overall, our data suggest that signals originating at the plasma membrane play a dominant role in sustained V 2 R signaling stimulated by arginine vasopressin.
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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 | 0.001 |
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".