ArticleAnnals of neurology2016
Mutation-specific effects on thin filament length in thin filament myopathy.
Article in Annals of neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 71 citations in OpenAlex.
- Klhl41b orchestrates sarcomere assembly and growth to drive skeletal muscle hypertrophy in vivo.Skeletal muscle · 2026Article
- The hallmarks of skeletal muscle health.Nature metabolism · 2026Review
- Renaissance at the actin filament pointed end: Mechanisms of assembly, capping and depolymerization.Current opinion in cell biology · 2026Review
- Actin Filament Pointed Ends: Assays for Regulation of Assembly and Disassembly by Tropomodulin and Tropomyosin.Cytoskeleton (Hoboken, N.J.) · 2025Article
- Retrospective Cohort Analysis of Clinical, Molecular, and Histopathologic Characteristics of 275 Patients With Nemaline Myopathy.Neurology. Genetics · 2025Article
- Prediction and biological significance of small changes in binding of leiomodin to tropomyosin.The Journal of general physiology · 2025Article
- Article
- Dilated cardiomyopathy-associated skeletal muscle actin (ACTA1) mutation R256H disrupts actin structure and function and causes cardiomyocyte hypocontractility.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Dominantly inherited muscle disorders: understanding their complexity and exploring therapeutic approaches.Disease models & mechanisms · 2024Review
- Congenital myopathies: pathophysiological mechanisms and promising therapies.Journal of translational medicine · 2024Review
- Characterization of NEB pathogenic variants in patients reveals novel nemaline myopathy disease mechanisms and omecamtiv mecarbil force effects.Acta neuropathologica · 2024Article
- Tirasemtiv enhances submaximal muscle tension in an Acta1:p.Asp286Gly mouse model of nemaline myopathy.The Journal of general physiology · 2024Article
- Recessive TMOD1 mutation causes childhood cardiomyopathy.Communications biology · 2024Article
- An Update on Reported Variants in the Skeletal MuscleHuman mutation · 2024Review
- A nemaline myopathy-linked mutation inhibits the actin-regulatory functions of tropomodulin and leiomodin.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Drosophila Tropomodulin is required for multiple actin-dependent processes within developing myofibers.Development (Cambridge, England) · 2023Article
- Actin polymerization and depolymerization in developing vertebrates.Frontiers in physiology · 2023Review
- NEB mutations disrupt the super-relaxed state of myosin and remodel the muscle metabolic proteome in nemaline myopathy.Acta neuropathologica communications · 2022Article
- Removal of MuRF1 Increases Muscle Mass in Nemaline Myopathy Models, but Does Not Provide Functional Benefits.International journal of molecular sciences · 2022Article
- Molecular and cellular basis of genetically inherited skeletal muscle disorders.Nature reviews. Molecular cell biology · 2021Review
Corrections and comments
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Authors and funding
23 authors at 13 institutions in 6 countries.
Funding
Abstract
objectiveThin filament myopathies are among the most common nondystrophic congenital muscular disorders, and are caused by mutations in genes encoding proteins that are associated with the skeletal muscle thin filament. Mechanisms underlying muscle weakness are poorly understood, but might involve the length of the thin filament, an important determinant of force generation.
methodsWe investigated the sarcomere length-dependence of force, a functional assay that provides insights into the contractile strength of muscle fibers as well as the length of the thin filaments, in muscle fibers from 51 patients with thin filament myopathy caused by mutations in NEB, ACTA1, TPM2, TPM3, TNNT1, KBTBD13, KLHL40, and KLHL41.
resultsLower force generation was observed in muscle fibers from patients of all genotypes. In a subset of patients who harbor mutations in NEB and ACTA1, the lower force was associated with downward shifted force-sarcomere length relations, indicative of shorter thin filaments. Confocal microscopy confirmed shorter thin filaments in muscle fibers of these patients. A conditional Neb knockout mouse model, which recapitulates thin filament myopathy, revealed a compensatory mechanism; the lower force generation that was associated with shorter thin filaments was compensated for by increasing the number of sarcomeres in series. This allowed muscle fibers to operate at a shorter sarcomere length and maintain optimal thin-thick filament overlap.
interpretationThese findings might provide a novel direction for the development of therapeutic strategies for thin filament myopathy patients with shortened thin filament lengths. Ann Neurol 2016;79:959-969.
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