Cardiac myofilament regulation by protein phosphatase type 1α and CapZ
Bibliographic record
Abstract
Myofilament regulation by protein kinases is well characterized, but relatively little is known about protein phosphatase control of myofilaments. Increased protein phosphatase type 1 (PP1) activity observed in failing hearts underscores the need for investigation of this intracellular signal, including the elements that regulate its activity. The Z-disc protein CapZ controls protein kinase C (PKC) regulation of cardiac myofilaments, but whether this effect is specific to PKC, or CapZ plays a general role in intracellular signalling, is not known. We sought to determine how the alpha isoform of PP1 (PP1alpha) regulates murine cardiac myofilaments and whether CapZ influences PP1alpha-dependent regulation of cardiac myofilaments. Immunoblot analysis showed PP1alpha binding to cardiac myofilaments. Exogenous PP1alpha increased myofilament Ca2+ sensitivity and maximal actomyosin Mg2+-ATPase activity while dephosphorylating myosin binding protein C, troponin T, troponin I, and myosin light chain 2. Extraction of CapZ decreased myofilament-associated PP1alpha and attenuated the effects of PP1alpha on myofilament activation. PP1alpha-dependent dephosphorylation of myofilament proteins was reduced with CapZ extraction, except for troponin I. Extracting CapZ after PP1alpha treatment allowed most of the PP1alpha-dependent effects on myofilament activation to remain, indicating that CapZ removal modestly desensitizes cardiac myofilaments to dephosphorylation. Our results demonstrate myofilament regulation by PP1alpha and support the concept that cardiac Z-discs are vital components in intracellular signalling.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".