ArticleMolecular biology of the cell2014
Calpain-mediated proteolysis of tropomodulin isoforms leads to thin filament elongation in dystrophic skeletal muscle.
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.
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Who cites it
23 citing papers in PubMed, 32 citations in OpenAlex.
- Mechanism of actin thin filament pointed-end elongation by leiomodin.Nature communications · 2026Article
- Genome-Wide Association Study of Conformation Traits in Brazilian Holstein Cattle.Animals : an open access journal from MDPI · 2024Article
- Proteolytic degradation of atrial sarcomere proteins underlies contractile defects in atrial fibrillation.American journal of physiology. Heart and circulatory physiology · 2024Article
- SERCA2a overexpression improves muscle function in a canine Duchenne muscular dystrophy model.Molecular therapy. Methods & clinical development · 2024Article
- The Mechanisms of Thin Filament Assembly and Length Regulation in Muscles.International journal of molecular sciences · 2022Review
- Relationship of intracellular proteolysis with CAP1 and cofilin1 in non-small-cell lung cancer.Journal of biosciences · 2021Article
- Under construction: The dynamic assembly, maintenance, and degradation of the cardiac sarcomere.Journal of molecular and cellular cardiology · 2020Review
- Tropomodulins Control the Balance between Protrusive and Contractile Structures by Stabilizing Actin-Tropomyosin Filaments.Current biology : CB · 2020Article
- Assembly and Maintenance of Sarcomere Thin Filaments and Associated Diseases.International journal of molecular sciences · 2020Review
- Molecular Insights into Muscle Homeostasis, Atrophy and Wasting.Current genomics · 2018Review
- Tropomodulins and Leiomodins: Actin Pointed End Caps and Nucleators in Muscles.Biophysical journal · 2017Review
- Tubules of plant reoviruses exploit tropomodulin to regulate actin-based tubule motility in insect vector.Scientific reports · 2017Article
- Aberrant developmental titin splicing and dysregulated sarcomere length in Thymosin β4 knockout mice.Journal of molecular and cellular cardiology · 2017Article
- Software-based measurement of thin filament lengths: an open-source GUI for Distributed Deconvolution analysis of fluorescence images.Journal of microscopy · 2017Article
- Feisty filaments: actin dynamics in the red blood cell membrane skeleton.Current opinion in hematology · 2016Review
- iTRAQ-based proteomic analysis of myofibrillar contents and relevant synthesis and proteolytic proteins in soleus muscle of hibernating Daurian ground squirrels (Proteome science · 2016Article
- Role of Active Contraction and Tropomodulins in Regulating Actin Filament Length and Sarcomere Structure in Developing Zebrafish Skeletal Muscle.Frontiers in physiology · 2016Article
- Tropomodulin 1 directly controls thin filament length in both wild-type and tropomodulin 4-deficient skeletal muscle.Development (Cambridge, England) · 2015Article
- Article
- Fluid Shear Stress Upregulates E-Tmod41 via miR-23b-3p and Contributes to F-Actin Cytoskeleton Remodeling during Erythropoiesis.PloS one · 2015Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
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.
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