Roles of Rab1 GTPase and dimerization in the cell surface transport of angiotensin II type 2 receptor
Bibliographic record
Abstract
The physiological function of angiotensin II (Ang II) is mediated through Ang II type 1 (AT1R) and type 2 (AT2R) receptors. Our previous studies indicate that AT1R plasma membrane expression is regulated by Rab and Sar1 GTPases and the C‐terminal F(X)6LL motif. However, the molecular mechanisms of the export trafficking of AT2R remain poorly defined. Here we report that cell‐surface expression of AT2R was markedly augmented by Rab1 and attenuated by dominant negative Rab1 mutants (S25N and N124I) and siRNA‐mediated Rab1 depletion. The Rab1 mutants also inhibited the overall expression of AT2R, but not AT1R, likely via promoting ubiquitin‐mediated degradation of ER‐accumulated AT2R. Consistently, AT2R‐mediated inhibition of EGF‐activated ERK1/2 was significantly reduced by the Rab1 mutants, indicating that endogenous Rab1 controls the cell surface targeting and signaling of AT2R. Furthermore, ER‐export deficient AT1R mutant, in which the F(X)6LL motif were mutated, formed both homodimers and heterodimers with AT2R, which blocked AT2R trafficking to the cell surface, suggesting constitutive dimerization of both receptors in the ER and an important role of dimerization in ER export. These data demonstrate that nascent AT2R transport from the ER to its functional destination is a highly regulated process and its signaling can be manipulated by modifying its biosynthesis (R01GM076167).
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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) | 0.000 | 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 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".