Phosphorylation and hetero‐oligomerization regulate the dopamine D3 receptor/adenylyl cyclase type 5 signaling complex
Bibliographic record
Abstract
The dopamine D3 receptor (D3R) is a seven‐transmembrane‐spanning protein mediating its intracellular effects through the activation of heterotrimeric Gi/o proteins. The D3R‐mediated Gi/o protein activation culminates in an isoform‐specific inhibition of adenylyl cyclase type 5 (AC5) as previously demonstrated using a co‐transfection approach. In the present study, we explore the role of phosphorylation and hetero‐oligomerization in regulating the functional interplay between D3R and AC5 in co‐transfected human embryonic kidney 293 (HEK293) cells using immunoprecipitation, whole cell phosphorylation and cAMP assays. Whole cell phosphorylation experiments show that D3R exhibits basal and dopamine‐induced phosphorylation in cells not expressing AC5. Interestingly, our preliminary studies demonstrate that D3R is dephosphorylated in AC5‐expressing HEK293 cells following dopamine exposure. Moreover, our co‐immunoprecipitation studies imply that D3R and AC5 form hetero‐oligomers under basal conditions. However, dopamine stimulation curtails the D3R‐AC5 hetero‐oligomerization. Overall, our work suggests a novel paradigm in 7TMR‐mediated signaling whereby the phosphorylation of a 7TMR under steady‐state conditions and following agonist stimulation differentially regulate the hetero‐oligomerization process between the receptor and its effector. Supported by CIHR (MOP‐84442; MT).
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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) | 0.001 | 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".