Molecular and cellular events of dopamine D1 receptor‐mediated tau phosphorylation in SK‐N‐MC cells
Bibliographic record
Abstract
Microtubules are involved in the formation of axons and dendrites, maintenance of neuronal morphology, and cellular trafficking. Recent studies suggest that drugs affecting dopamine activity in the brain can induce cytoskeletal modifications. For instance, we have demonstrated in acute rat brain slices a molecular chain of events connecting dopamine D1 receptor to aberrant phosphorylation of the microtubule-associated protein tau. However, the molecular and cellular effects of tau phosphorylated by means of the activation of dopamine receptors were unexplored. Here we used SK-N-MC cells, which express endogenously functional D1 receptors, to demonstrate that levels of phosphorylated tau at serines 199-202 or 214 are increased by a calcium-dependent pathway subsequent to D1 receptor stimulation. Using selective pharmacological tools, we showed that enhanced intracellular calcium lead to cyclin-dependent kinase 5 (cdk5) activation, by calpain proteolysis of p35 to p25, as well as glycogen synthase kinase 3β (GSK3β) activation, by its phosphorylation at tyrosine 216. Interestingly, while the activation of protein kinase A (PKA) led directly to the phosphorylation of tau at serine 214, tau phosphorylation at serines 199-202 was independent of PKA. In addition, inhibition of cdk5 or GSK3β prevented the decrease in cell viability induced by D1 receptor stimulation whereas PKA inhibition had no influence. Our data demonstrate that activation of cdk5 and GSK3β following D1 receptor stimulation could have profound influence on both the neuronal cytoskeletal constituent tau and cell survival in SK-N-MC cells.
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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".