New insights into mechanisms of nuclear translocation of G-protein coupled receptors
Bibliographic record
Abstract
The G-protein coupled receptor (GPCR) signaling was long believed to involve activation of receptor exclusively at the cell surface, followed by its binding to heterotrimeric G-proteins and arrestins to trigger various intracellular signaling cascades, and termination of signaling by internalization of the receptor. It is now accepted that many GPCRs continue to signal after internalization in the endosomes. Since the breakthrough discoveries of nuclear binding sites for their ligands in 1980s, several GPCRs have been detected at cell nuclei. But mechanisms of nuclear localization of GPCRs, many of whom contain putative nuclear localization signals, remain poorly understood to date. Nevertheless, it is known that subcellular trafficking of GPCRs is regulated by members of Ras superfamily of small GTPases, most notably by Rab and Arf GTPases. In this commentary, we highlight several recent studies which suggest novel roles of small GTPases, importins and sorting nexin proteins in the nuclear translocation of GPCRs via vesicular transport pathways. Taken together with increasing evidence for in vivo functionality of the nuclear GPCRs, better understanding of their trafficking will provide valuable clues in cell biology.
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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) | 0.001 | 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".