Evidence map›Paper›PMID 24430868›Full record

ArticleMolecular biology of the cell2014

Calpain-mediated proteolysis of tropomodulin isoforms leads to thin filament elongation in dystrophic skeletal muscle.

David S Gokhin, Matthew T Tierney, Zhenhua Sui, Alessandra Sacco, Velia M Fowler

Abstract read
In one paragraph

Article in Molecular biology of the cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
2.7field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

23 citing papers in PubMed, 32 citations in OpenAlex.

  1. Article
  2. Article
  3. Proteolytic degradation of atrial sarcomere proteins underlies contractile defects in atrial fibrillation.American journal of physiology. Heart and circulatory physiology · 2024
    Article
  4. Article
  5. The Mechanisms of Thin Filament Assembly and Length Regulation in Muscles.International journal of molecular sciences · 2022
    Review
  6. Article
  7. Review
  8. Article
  9. Review
  10. Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

David S GokhinDepartment of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037 Sanford Children's Health Research Center, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037.
Matthew T Tierney
Zhenhua Sui
Alessandra Sacco
Velia M Fowler
Scripps Research Institute · USSanford Burnham Prebys Medical Discovery Institute · US

Funding

Capping Actin Growth in Erythroid and Nonerythroid CellsR01HL083464 · NHLBI · UNIVERSITY OF DELAWARE · PI FOWLER, VELIA M · 2006 to 2019
$7.1M
Core--ProteomicsP30EY012598 · NEI · SCRIPPS RESEARCH INSTITUTE · PI FRIEDLANDER, MARTIN · 2001 to 2005
$3.6M
San Diego Skeletal Muscle Research CenterP30AR061303 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHEN, JU · 2011 to 2015
$3.3M
Role of proteoglycan sulfation during muscle regeneration in dystrophic animalsF31AR065923 · NIAMS · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI TIERNEY, MATTHEW · 2014 to 2016
$63k
NEI NIH HHS P30 EY012598NHLBI NIH HHS R01 HL083464NHLBI NIH HHS R01-HL083464NIAMS NIH HHS F31 AR065923NIAMS NIH HHS P30 AR061303NIAMS NIH HHS P30-AR061303
6 · The paper itself

Abstract

Duchenne muscular dystrophy (DMD) induces sarcolemmal mechanical instability and rupture, hyperactivity of intracellular calpains, and proteolytic breakdown of muscle structural proteins. Here we identify the two sarcomeric tropomodulin (Tmod) isoforms, Tmod1 and Tmod4, as novel proteolytic targets of m-calpain, with Tmod1 exhibiting ∼10-fold greater sensitivity to calpain-mediated cleavage than Tmod4 in situ. In mdx mice, increased m-calpain levels in dystrophic soleus muscle are associated with loss of Tmod1 from the thin filament pointed ends, resulting in ∼11% increase in thin filament lengths. In mdx/mTR mice, a more severe model of DMD, Tmod1 disappears from the thin filament pointed ends in both tibialis anterior (TA) and soleus muscles, whereas Tmod4 additionally disappears from soleus muscle, resulting in thin filament length increases of ∼10 and ∼12% in TA and soleus muscles, respectively. In both mdx and mdx/mTR mice, both TA and soleus muscles exhibit normal localization of α-actinin, the nebulin M1M2M3 domain, Tmod3, and cytoplasmic γ-actin, indicating that m-calpain does not cause wholesale proteolysis of other sarcomeric and actin cytoskeletal proteins in dystrophic skeletal muscle. These results implicate Tmod proteolysis and resultant thin filament length misspecification as novel mechanisms that may contribute to DMD pathology, affecting muscles in a use- and disease severity-dependent manner.

Indexed as

Actin CytoskeletonActininActinsAnimalsCalpainDisease Models, AnimalMiceMice, Inbred mdxMuscle ProteinsMuscle, SkeletalMuscular Dystrophy, DuchenneProtein Structure, TertiaryProteolysisTropomodulinActininActinsCalpainm-calpainMuscle ProteinsnebulinTmod1 protein, mouseTmod3 protein, mouseTmod4 protein, mouseTropomodulin

Identifiers

PMID24430868
PMCPMC3952854
OpenAlexW2150570809

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.