Heterodimerization of V1a and V2 vasopressin receptors determines the interaction with β-arrestin and their trafficking patterns
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
V1a vasopressin receptor (V1aR) and V2 vasopressin receptor (V2R) present distinct mechanisms of agonist-promoted trafficking. Although both receptors are endocytosed by way of beta-arrestin-dependent processes, beta-arrestin dissociates rapidly from V1aR, allowing its rapid recycling to the plasma membrane while beta-arrestin remains associated with V2R in the endosomes, leading to their intracellular accumulation. Here, we demonstrate that, when coexpressed, the two receptors can be endocytosed as stable heterodimers. On activation with a nonselective agonist, both receptors cotrafficked with beta-arrestin in endosomes where the stable interaction inhibited the recycling of V1aR to the plasma membrane, thus conferring a V2R-like endocytotic/recycling pattern to the V1aR/V2R heterodimer. Coexpression of the constitutively internalized R137HV2R mutant with V1aR was sufficient to promote cointernalization of V1aR in beta-arrestin-positive vesicles even in the absence of agonist stimulation. This finding indicates that internalization of the heterodimer does not require activation of each of the protomers. Consistent with this notion, a V1aR-selective agonist led to the coendocytosis of V2R. In that case, however, the V1aR/V2R heterodimer was not stably associated with beta-arrestin, and both receptors were recycled back to the cell surface, indicating that the complex followed the V1aR endocytotic/recycling path. Taken together, these results suggest that heterodimerization regulates the endocytotic processing of G protein-coupled receptors and that the identity of the activated protomer within the heterodimer determines the fate of the internalized receptors.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 it