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 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".