Identifying a role of the actin capping protein <scp>C</scp>ap<scp>Z</scp> in β‐adrenergic receptor signalling
Bibliographic record
Abstract
AIM: β-Adrenergic receptor activation increases myocardial contractility, in part through protein kinase A (PKA)-dependent modification of cardiac myofilaments. PKA regulation of cardiac myofilaments is contingent influenced by protein kinase C (PKC) phosphorylation of troponin I (TnI). Reductions in the cardiac Z-disc protein CapZ attenuate PKC regulation of myofilament activation. We hypothesized that CapZ-deficient transgenic mouse hearts respond poorly to β-adrenergic receptor activation, as a result of impaired PKC activation. METHODS: Wild-type and CapZ-deficient transgenic mice were treated with the β-adrenergic receptor agonist isoproterenol (ISO) and whole heart function assessed by echocardiography. Cardiac myofilaments were isolated post-ISO treatment and subjected to an actomyosin MgATPase assay and protein phosphorylation gels. RESULTS: CapZ-deficient transgenic mouse hearts exhibited increased contractility and myofilament calcium sensitivity at baseline, as compared to wild-type mice. In wild-type mice, ISO increased myocardial contractility and decreased myofilament calcium sensitivity, along with an increase in TnI phosphorylation. CapZ-deficient transgenic mice responded to ISO treatment, and myocardial functional differences between transgenic and wild-type mice were abolished. ISO-dependent changes in myofilament activation in transgenic mice were similar to those observed in wild-type. TnI phosphorylation was similarly increased in wild-type and transgenic mice following ISO treatment, while CapZ-deficient transgenic mouse myofilaments also exhibited increased myosin-binding protein C phosphorylation. Differences in myofilament protein phosphorylation patterns suggest the intracellular mechanisms utilized by β-adrenergic receptor activation are different than that seen in wild-type hearts. CONCLUSIONS: These data further support the concept that the cardiac Z-disc protein is a regulator of myofilament function and intracellular signalling transduction.
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| 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".