ArticleMolecular biology of the cell2019
Reductions in ATPase activity, actin sliding velocity, and myofibril stability yield muscle dysfunction in Drosophila models of myosin-based Freeman-Sheldon syndrome.
Article in Molecular biology of the cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 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
13 citing papers in PubMed, 16 citations in OpenAlex.
- Article
- UNC-45 assisted myosin folding depends on a conserved FXNature communications · 2024Article
- Homologous mutations in human β, embryonic, and perinatal muscle myosins have divergent effects on molecular power generation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Musculoskeletal defects associated with myosin heavy chain-embryonic loss of function are mediated by the YAP signaling pathway.EMBO molecular medicine · 2023Article
- Myosin Transducer Inter-Strand Communication Is Critical for Normal ATPase Activity and Myofibril Structure.Biology · 2022Article
- The R369 Myosin Residue within Loop 4 Is Critical for Actin Binding and Muscle Function inInternational journal of molecular sciences · 2022Article
- A Genomic Approach to Delineating the Occurrence of Scoliosis in Arthrogryposis Multiplex Congenita.Genes · 2021Article
- Prolonged myosin binding increases muscle stiffness in Drosophila models of Freeman-Sheldon syndrome.Biophysical journal · 2021Article
- MYH3-associated distal arthrogryposis zebrafish model is normalized with para-aminoblebbistatin.EMBO molecular medicine · 2020Article
- A Novel Mechanism for Activation of Myosin Regulatory Light Chain by Protein Kinase C-Delta inGenetics · 2020Article
- Drosophila myosin mutants model the disparate severity of type 1 and type 2B distal arthrogryposis and indicate an enhanced actin affinity mechanism.Skeletal muscle · 2020Article
- Myosin heavy chain-embryonic regulates skeletal muscle differentiation during mammalian development.Development (Cambridge, England) · 2020Article
- X-ray Crystallographic and Molecular Dynamic Analyses of Drosophila melanogaster Embryonic Muscle Myosin Define Domains Responsible for Isoform-Specific Properties.Journal of molecular biology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Using Drosophila melanogaster, we created the first animal models for myosin-based Freeman-Sheldon syndrome (FSS), a dominant form of distal arthrogryposis defined by congenital facial and distal skeletal muscle contractures. Electron microscopy of homozygous mutant indirect flight muscles showed normal (Y583S) or altered (T178I, R672C) myofibril assembly followed by progressive disruption of the myofilament lattice. In contrast, all alleles permitted normal myofibril assembly in the heterozygous state but caused myofibrillar disruption during aging. The severity of myofibril defects in heterozygotes correlated with the level of flight impairment. Thus our Drosophila models mimic the human condition in that FSS mutations are dominant and display varied degrees of phenotypic severity. Molecular modeling indicates that the mutations disrupt communication between the nucleotide-binding site of myosin and its lever arm that drives force production. Each mutant myosin showed reduced in vitro actin sliding velocity, with the two more severe alleles significantly decreasing the catalytic efficiency of actin-activated ATP hydrolysis. The observed reductions in actin motility and catalytic efficiency may serve as the mechanistic basis of the progressive myofibrillar disarray observed in the Drosophila models as well as the prolonged contractile activity responsible for skeletal muscle contractures in FSS patients.
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.