Cell-to-cell variations in subcellular localisation of V2R are independent of its expression level
Bibliographic record
Abstract
Abstract G protein coupled receptors (GPCRs) translate the actions of hormones into intracellular signalling events. Mutations in GPCRs can prevent their correct expression and trafficking to the cell surface and cause disease. We use single cell measurements in HEK293 cells to show that the balance between endoplasmic reticulum (ER) and cell surface localisation of the Vasopressin 2 receptor (V2R) varies significantly from cell to cell. We find that mutations in the V2R affect the proportion of cells able to send this GPCR to the cell surface but do not prevent all cells in the population from correctly trafficking the mutant receptors. These findings reveal that the ability of cells to correctly traffic V2R to the cell surface depends not only on the expressed V2R mutant but also on the individual cell environment. Significance statement Missense mutations in the Vasopressin 2 Receptor (V2R) cause Nephrogenic Diabetes Insipidus. Some of these mutations prevent correct expression and trafficking of V2R to the cell surface resulting in a loss-of-function. We show -using single cell measurements-that the balance between endoplasmic reticulum and cell surface localisation of the V2R varies significantly from cell to cell, independent from its expression level. Mutations affect the proportion of cells able to send V2R to the cell surface but do not prevent all cells in the population from correctly trafficking the mutant receptors. Hence, the ability of cells to correctly traffic V2R to the cell surface depends not only on expressed V2R mutant but also on the cell environment.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".