ArticleThe Journal of general physiology2019
Nebulin and titin modulate cross-bridge cycling and length-dependent calcium sensitivity.
Article in The Journal of general physiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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27 citing papers in PubMed, 40 citations in OpenAlex.
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- Design Principles and Benefits of Spatially Explicit Models of Myofilament Function.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Load sharing between synergistic muscles characterized by a ligand-binding approach and elastography.Scientific reports · 2023Article
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- Nucleus Mechanosensing in Cardiomyocytes.International journal of molecular sciences · 2023Review
- Using Multiscale Simulations as a Tool to Interpret Equatorial X-ray Fiber Diffraction Patterns from Skeletal Muscle.International journal of molecular sciences · 2023Article
- Axial stress determines the velocity of shear wave propagation in passive but not active muscles in vivo.Journal of applied physiology (Bethesda, Md. : 1985) · 2023Article
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- Functional and structural differences between skinned and intact muscle preparations.The Journal of general physiology · 2022Review
- Effect of Myosin Isoforms on Cardiac Muscle Twitch of Mice, Rats and Humans.International journal of molecular sciences · 2022Article
- Muscle Actuators, Not Springs, Drive Maximal Effort Human Locomotor Performance.Journal of sports science & medicine · 2021Article
- Molecular and cellular basis of genetically inherited skeletal muscle disorders.Nature reviews. Molecular cell biology · 2021Review
- Effect of Active Lengthening and Shortening on Small-Angle X-ray Reflections in Skinned Skeletal Muscle Fibres.International journal of molecular sciences · 2021Article
- The effect of variable troponin C mutation thin filament incorporation on cardiac muscle twitch contractions.Journal of molecular and cellular cardiology · 2021Article
- Mechanisms of Frank-Starling law of the heart and stretch activation in striated muscles may have a common molecular origin.Journal of muscle research and cell motility · 2021Article
- Multiscale modeling of twitch contractions in cardiac trabeculae.The Journal of general physiology · 2021Article
- Inhibition of Histone Deacetylases 4 and 5 Reduces Titin Proteolysis and Prevents Reduction of TTN Gene Expression in Atrophied Rat Soleus Muscle after Seven-Day Hindlimb Unloading.Doklady. Biochemistry and biophysics · 2020Article
- Triggering typical nemaline myopathy with compound heterozygous nebulin mutations reveals myofilament structural changes as pathomechanism.Nature communications · 2020Article
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7 authors at 5 institutions in 3 countries.
Funding
Abstract
Various mutations in the structural proteins nebulin and titin that are present in human disease are known to affect the contractility of striated muscle. Loss of nebulin is associated with reduced actin filament length and impairment of myosin binding to actin, whereas titin is thought to regulate muscle passive elasticity and is likely involved in length-dependent activation. Here, we sought to assess the modulation of muscle function by these sarcomeric proteins by using the computational platform muscle simulation code (MUSICO) to quantitatively separate the effects of structural changes, kinetics of cross-bridge cycling, and calcium sensitivity of the thin filaments. The simulations show that variation in thin filament length cannot by itself account for experimental observations of the contractility in nebulin-deficient muscle, but instead must be accompanied by a decreased myosin binding rate. Additionally, to match the observed calcium sensitivity, the rate of TnI detachment from actin needed to be increased. Simulations for cardiac muscle provided quantitative estimates of the effects of different titin-based passive elasticities on muscle force and activation in response to changes in sarcomere length and interfilament lattice spacing. Predicted force-pCa relations showed a decrease in both active tension and sensitivity to calcium with a decrease in passive tension and sarcomere length. We conclude that this behavior is caused by partial redistribution of the muscle load between active muscle force and titin-dependent passive force, and also by redistribution of stretch along the thin filament, which together modulate the release of TnI from actin. These data help advance understanding of how nebulin and titin mutations affect muscle function.
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