Expression of the Dystrophin‐Associated Protein Complex in the Absence of Skeletal Muscle AMPK
Bibliographic record
Abstract
The dystrophin‐associated protein complex (DAPC) is composed of proteins that are highly expressed along the sarcolemma. The DAPC provides a mechanical link between the intracellular cytoskeleton and extracellular matrix, as well as a signal transduction apparatus from the periphery to the interior of muscle fibers. The signalling molecule AMP‐activated protein kinase (AMPK) is a powerful regulator of phenotypic plasticity. Recent evidence has shown that chronic AMPK activation alters the expression of DAPC components. However, a more comprehensive understanding of the influence of AMPK on the DAPC is lacking. Therefore, the purpose of this study was to investigate the role of AMPK in the expression of the DAPC. Extensor digitorum longus (EDL) and soleus (SOL) muscles representing fast glycolytic and slow oxidative tissues, respectively, were obtained from wild‐type (WT) mice, as well as from mice deficient in both isoforms of the AMPK‐β subunit in skeletal muscle (AMPK‐MKO). RT‐PCR and Western blotting measured mRNA and protein content of DAPC components, respectively. In WT animals, utrophin and laminin mRNA expression, as well as laminin and β‐dystroglycan protein content were ~25–60% higher (p < 0.05) in the SOL versus EDL muscle. In contrast, neuronal nitric oxide synthase (nNOS) mRNA was 60% lower in SOL. The AMPK‐MKO animals displayed a different pattern of fiber‐type specific expression of DAPC components. In these mice, laminin, γ‐sarcoglycan (SG), dystrophin, and utrophin transcripts, as well as dystrophin and utrophin protein expression were 40–55% greater (p < 0.05) in the SOL versus the EDL. β‐SG and nNOS mRNA content were lower in the EDL muscle of AMPK‐MKO mice, as compared to their WT counterparts. We also assessed the expression of peroxisome proliferator activated receptor coactivator‐1α (PGC‐1α) and Ca 2+ /calmodulin dependent protein kinase II (CAMKII), factors that contribute to the upstream regulation of the DAPC. PGC‐1α mRNA content was higher in SOL relative to EDL muscles of both genotypes. CAMKIIα protein expression was significantly lower in SOL muscles versus EDL muscles of WT and AMPK‐MKO, while CAMKIIβ exhibited the opposite pattern. PGC‐1α mRNA tended to be higher in the muscles from AMPK‐MKO mice compared to WT animals. Conversely, CAMKII mRNA content tended to be reduced in the AMPK‐MKO muscles, as compared to WT. These data indicate a fiber‐type specificity to DAPC expression in skeletal muscle. Furthermore, AMPK deficiency results in a differential profile of DAPC components, as well as in alternations in the expression of alternative upstream DAPC regulators. Our results suggest that AMPK contributes to the expression profile of the DAPC. Support or Funding Information Natural Sciences and Engineering Research Council of Canada, Canada Research Chairs
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".