ArticlePloS one2012
Nemaline myopathy-related skeletal muscle α-actin (ACTA1) mutation, Asp286Gly, prevents proper strong myosin binding and triggers muscle weakness.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- Paraspinal muscle fibre structural and contractile characteristics demonstrate distinct irregularities in patients with spinal degeneration and deformity.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2024Article
- Congenital myopathies: pathophysiological mechanisms and promising therapies.Journal of translational medicine · 2024Review
- Aberrant myonuclear domains and impaired myofiber contractility despite marked hypertrophy in MYMK-related, Carey-Fineman-Ziter Syndrome.Acta neuropathologica communications · 2024Article
- Tirasemtiv enhances submaximal muscle tension in an Acta1:p.Asp286Gly mouse model of nemaline myopathy.The Journal of general physiology · 2024Article
- An Update on Reported Variants in the Skeletal MuscleHuman mutation · 2024Review
- Pharmacological Inhibition of Myostatin in a Mouse Model of Typical Nemaline Myopathy Increases Muscle Size and Force.International journal of molecular sciences · 2023Article
- Myofibre Hyper-Contractility in Horses Expressing the Myosin Heavy Chain Myopathy Mutation,Cells · 2021Article
- Myopathy-Sensitive G-Actin Segment 227-235 Is Involved in Salt-Induced Stabilization of Contacts within the Actin Filament.International journal of molecular sciences · 2021Article
- Nebulin nemaline myopathy recapitulated in a compound heterozygous mouse model with both a missense and a nonsense mutation in Neb.Acta neuropathologica communications · 2020Article
- Impairments in contractility and cytoskeletal organisation cause nuclear defects in nemaline myopathy.Acta neuropathologica · 2019Article
- Nemaline myopathies: a current view.Journal of muscle research and cell motility · 2019Review
- Prelamin A causes aberrant myonuclear arrangement and results in muscle fiber weakness.JCI insight · 2018Article
- Myostatin inhibition using mRK35 produces skeletal muscle growth and tubular aggregate formation in wild type and TgACTA1D286G nemaline myopathy mice.Human molecular genetics · 2018Article
- Dysfunctional sarcomere contractility contributes to muscle weakness in ACTA1-related nemaline myopathy (NEM3).Annals of neurology · 2018Article
- Molecular Consequences of the Myopathy-Related D286G Mutation on Actin Function.Frontiers in physiology · 2018Article
- Modulating myosin restores muscle function in a mouse model of nemaline myopathy.Annals of neurology · 2016Article
- Zebrafish models for nemaline myopathy reveal a spectrum of nemaline bodies contributing to reduced muscle function.Acta neuropathologica · 2015Article
- Pathophysiological concepts in the congenital myopathies: blurring the boundaries, sharpening the focus.Brain : a journal of neurology · 2015Review
- Tropomodulins and tropomyosins: working as a team.Journal of muscle research and cell motility · 2013Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Many mutations in the skeletal muscle α-actin gene (ACTA1) lead to muscle weakness and nemaline myopathy. Despite increasing clinical and scientific interest, the molecular and cellular pathogenesis of weakness remains unclear. Therefore, in the present study, we aimed at unraveling these mechanisms using muscles from a transgenic mouse model of nemaline myopathy expressing the ACTA1 Asp286Gly mutation. We recorded and analyzed the mechanics of membrane-permeabilized single muscle fibers. We also performed molecular energy state computations in the presence or absence of Asp286Gly. Results demonstrated that during contraction, the Asp286Gly acts as a "poison-protein" and according to the computational analysis it modifies the actin-actin interface. This phenomenon is likely to prevent proper myosin cross-bridge binding, limiting the fraction of actomyosin interactions in the strong binding state. At the cell level, this decreases the force-generating capacity, and, overall, induces muscle weakness. To counterbalance such negative events, future potential therapeutic strategies may focus on the inappropriate actin-actin interface or myosin binding.
Indexed as
Identifiers
What OpenQuestion holds
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.