Regulation of Angiotensin II Type 1A Receptor Intracellular Retention, Degradation, and Recycling by Rab5, Rab7, and Rab11 GTPases
Bibliographic record
Abstract
Previous studies have demonstrated that the interaction of the angiotensin II type 1A receptor (AT(1A)R) carboxyl-terminal tail with Rab5a may modulate Rab5a activity, leading to the homotypic fusion of endocytic vesicles. Therefore, we have investigated whether AT(1A)R/Rab5a interactions mediate the retention of AT(1A)R.beta-arrestin complexes in early endosomes and whether the overexpression of Rab7 and Rab11 GTPases influences AT(1A)R lysosomal degradation and plasma membrane recycling. We found that internalized AT(1A)R was retained in Rab5a-positive early endosomes and was neither targeted to lysosomes nor recycled back to the cell surface, whereas a mutant defective in Rab5a binding, AT(1A)R-(1-349), was targeted to lysosomes for degradation. However, the loss of Rab5a binding to the AT(1A)R carboxyl-terminal tail did not promote AT(1A)R recycling. Rather, it was the stable binding of beta-arrestin to the AT(1A)R that prevented, at least in part, AT(1A)R recycling. The overexpression of wild-type Rab7 and Rab7-Q67L resulted in both increased AT(1A)R degradation and AT(1A)R targeting to lysosomes. The Rab7 expression-dependent transition of "putative" AT(1A)R.beta-arrestin complexes to late endosomes was blocked by the expression of dominant-negative Rab5a-S34N. Rab11 overexpression established AT(1A)R recycling and promoted the redistribution of AT(1A)R.beta-arrestin complexes from early to recycling endosomes. Taken together, our data suggest that Rab5, Rab7, and Rab11 work in concert with one another to regulate the intracellular trafficking patterns of the AT(1A)R.
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How this classification was reachedexpand
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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".