ArticleProceedings of the National Academy of Sciences of the United States of America2018
Nebulin stiffens the thin filament and augments cross-bridge interaction in skeletal muscle.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- OXPHOS complex deficiency in congenital myopathy: A systematic review.European journal of clinical investigation · 2025Pooled it
- Distinct distributions of myosin motor conformations during contraction of slow and fast skeletal muscle.The Journal of physiology · 2026Article
- Mavacamten facilitates myosin head ON-to-OFF transitions and shortens thin filament length in relaxed mouse skeletal muscle.Physiological reports · 2025Article
- Structural variation in nebulin and its impact on phenotype and inheritance: establishing a dominant distal phenotype caused by large deletions.European journal of human genetics : EJHG · 2025Review
- Popping the hood of muscle motors using time-resolved, small-angle X-ray diffraction.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The distinctive mechanical and structural signatures of residual force enhancement in myofibers.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Congenital myopathies: pathophysiological mechanisms and promising therapies.Journal of translational medicine · 2024Review
- Comprehensive phenotypic characterization of an allelic series of zebrafish models of NEB-related nemaline myopathy.Human molecular genetics · 2024Article
- Cardiac myosin filaments are directly regulated by calcium.The Journal of general physiology · 2022Article
- Thick filament activation is different in fast- and slow-twitch skeletal muscle.The Journal of physiology · 2022Article
- Titin force in muscle cells alters lattice order, thick and thin filament protein formation.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Mitochondrial network configuration influences sarcomere and myosin filament structure in striated muscles.Nature communications · 2022Article
- Removal of MuRF1 Increases Muscle Mass in Nemaline Myopathy Models, but Does Not Provide Functional Benefits.International journal of molecular sciences · 2022Article
- Clinico-pathological features and mutational spectrum of 16 nemaline myopathy patients from a Chinese neuromuscular center.Acta neurologica Belgica · 2022Article
- The Mechanisms of Thin Filament Assembly and Length Regulation in Muscles.International journal of molecular sciences · 2022Review
- Small Angle X-ray Diffraction as a Tool for Structural Characterization of Muscle Disease.International journal of molecular sciences · 2022Review
- Analysis methods and quality criteria for investigating muscle physiology using x-ray diffraction.The Journal of general physiology · 2021Article
- The number of Z-repeats and super-repeats in nebulin greatly varies across vertebrates and scales with animal size.The Journal of general physiology · 2021Article
- Nebulin: Size matters for optimal muscle function.The Journal of general physiology · 2021Article
- Transcriptome Profiling Reveals Important Transcription Factors and Biological Processes in Skin Regeneration Mediated by Mechanical Stretch.Frontiers in genetics · 2021Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Nebulin is a giant sarcomeric protein that spans along the actin filament in skeletal muscle, from the Z-disk to near the thin filament pointed end. Mutations in nebulin cause muscle weakness in nemaline myopathy patients, suggesting that nebulin plays important roles in force generation, yet little is known about nebulin's influence on thin filament structure and function. Here, we used small-angle X-ray diffraction and compared intact muscle deficient in nebulin (using a conditional nebulin-knockout, Neb cKO) with control (Ctrl) muscle. When muscles were activated, the spacing of the actin subunit repeat (27 Å) increased in both genotypes; when converted to thin filament stiffness, the obtained value was 30 pN/nm in Ctrl muscle and 10 pN/nm in Neb cKO muscle; that is, the thin filament was approximately threefold stiffer when nebulin was present. In contrast, the thick filament stiffness was not different between the genotypes. A significantly shorter left-handed (59 Å) thin filament helical pitch was found in passive and contracting Neb cKO muscles, as well as impaired tropomyosin and troponin movement. Additionally, a reduced myosin mass transfer toward the thin filament in contracting Neb cKO muscle was found, suggesting reduced cross-bridge interaction. We conclude that nebulin is critically important for physiological force levels, as it greatly stiffens the skeletal muscle thin filament and contributes to thin filament activation and cross-bridge recruitment.
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