Dynamics of Actin‐based Structures in Migrating Artery Myocytes are Regulated by Phosphodiesterases
Bibliographic record
Abstract
The second messenger, cAMP, regulates vascular myocyte migration dichotomously. Indeed, while cAMP inhibits vascular myocyte migration in vitro and reduces intimal hyperplasia in vivo, it also promotes formation of integrin-based, actin-rich, leading edge projections in these cells; structures which are essential for migration. Our study was undertaken to examine if distinct cyclic nucleotide phosphodiesterases (PDEs) could modulate formation of such actin-rich projections in migrating mammary artery myocytes (MAM). Thus, we quantified formation of leading edge, actin-rich, structures in these cells and assessed how inhibiting or knocking down selected MAM PDEs (PDE1, PDE3 or PDE4) impacted their formation. In the absence of adenylyl cyclase activation, formation of these structures was promoted when either PDE1, or PDE4, were selectively inhibited using C-33 or Ro, 20-1724, respectively. PDE3 selective inhibition with cilostamide was without effect. In marked contrast, when added with forskolin, an adenylyl cyclase activator, PDE1, PDE3 or PDE4 inhibitors each potentiated the ability of forskolin to reduce formation of the actin-based structures. Knockdown of PDE1C or PDE4D, recapitulated effects observed with the enzyme inhibitors both in the absence and presence of forskolin. These data are consistent with the notion that localized cAMP “pools” regulated by PDE1 and/or PDE4 enzymes at the leading edges of migrating cells can promote formation of actin-based adhesive structures, but that these events are poorly supported in cells in which cAMP is globally increased.
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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".