ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2011
Disrupted myosin cross-bridge cycling kinetics triggers muscle weakness in nebulin-related myopathy.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 64 citations in OpenAlex.
- 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
- Comprehensive phenotypic characterization of an allelic series of zebrafish models of NEB-related nemaline myopathy.Human molecular genetics · 2024Article
- Characterization of NEB pathogenic variants in patients reveals novel nemaline myopathy disease mechanisms and omecamtiv mecarbil force effects.Acta neuropathologica · 2024Article
- Pharmacological Inhibition of Myostatin in a Mouse Model of Typical Nemaline Myopathy Increases Muscle Size and Force.International journal of molecular sciences · 2023Article
- NEB mutations disrupt the super-relaxed state of myosin and remodel the muscle metabolic proteome in nemaline myopathy.Acta neuropathologica communications · 2022Article
- Small Angle X-ray Diffraction as a Tool for Structural Characterization of Muscle Disease.International journal of molecular sciences · 2022Review
- Acute and chronic tirasemtiv treatment improves in vivo and in vitro muscle performance in actin-based nemaline myopathy mice.Human molecular genetics · 2021Article
- In vivo characterization of skeletal muscle function in nebulin-deficient mice.Muscle & nerve · 2020Article
- Nebulin: big protein with big responsibilities.Journal of muscle research and cell motility · 2020Review
- Nebulin nemaline myopathy recapitulated in a compound heterozygous mouse model with both a missense and a nonsense mutation in Neb.Acta neuropathologica communications · 2020Article
- The evolutionarily conserved C-terminal peptide of troponin I is an independently configured regulatory structure to function as a myofilament CaJournal of molecular and cellular cardiology · 2019Article
- Nebulin increases thin filament stiffness and force per cross-bridge in slow-twitch soleus muscle fibers.The Journal of general physiology · 2018Article
- Nebulin stiffens the thin filament and augments cross-bridge interaction in skeletal muscle.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Congenital myopathies: disorders of excitation-contraction coupling and muscle contraction.Nature reviews. Neurology · 2018Review
- Dysfunctional sarcomere contractility contributes to muscle weakness in ACTA1-related nemaline myopathy (NEM3).Annals of neurology · 2018Article
- Muscle Weakness in Rheumatoid Arthritis: The Role of CaEBioMedicine · 2017Review
- Novel myosin-based therapies for congenital cardiac and skeletal myopathies.Journal of medical genetics · 2016Review
- Mutation-specific effects on thin filament length in thin filament myopathy.Annals of neurology · 2016Article
- Nebulin, a multi-functional giant.The Journal of experimental biology · 2016Review
- Nebulin deficiency in adult muscle causes sarcomere defects and muscle-type-dependent changes in trophicity: novel insights in nemaline myopathy.Human molecular genetics · 2015Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 5 countries.
Funding
Abstract
Nebulin is a giant protein expressed at high levels in skeletal muscle. Mutations in the nebulin gene (NEB) lead to muscle weakness and various congenital myopathies. Despite increasing clinical and scientific interest, the pathogenesis of weakness remains unknown. The present study, therefore, aims at unraveling the underlying molecular mechanisms. Hence, we recorded and analyzed the mechanics as well as the X-ray diffraction patterns of human membrane-permeabilized single muscle fibers expressing nebulin mutations. Results demonstrated that, during contraction, the cycling rate of myosin heads attaching to actin is dramatically perturbed, causing a reduction in the fraction of myosin-actin interactions in the strong binding state. This phenomenon prevents complete thin-filament activation, more especially proper and full tropomyosin movement, further limiting additional binding of myosin cross-bridges. At the cell level, this reduces the force-generating capacity and, overall, provokes muscle weakness. To reverse such a negative cascade of events, future potential therapeutic interventions should, therefore, focus on the triggering component, the altered myosin cross-bridge cycling kinetics.
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Registered trials
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.