ArticleThe Journal of biological chemistry2012
Modular dispensability of dysferlin C2 domains reveals rational design for mini-dysferlin molecules.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. It is linked to trial NCT01863004 (Proteasomal Inhibition for Patients With Mis-sense Mutated Dysferlin), which is not on this map. Cited by 15 papers.
What it found
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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.
Proteasomal Inhibition for Patients With Mis-sense Mutated Dysferlin
Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- Whole Exome Sequencing Identified a Stop-Gained Mutation in DYSF Gene Associated With Dysferlinopathy in an Iranian Family.International journal of genomics · 2025Article
- The Dysferlinopathies Conundrum: Clinical Spectra, Disease Mechanism and Genetic Approaches for Treatments.Biomolecules · 2024Review
- Portrait of Dysferlinopathy: Diagnosis and Development of Therapy.Journal of clinical medicine · 2023Review
- Analysis of Dysferlin Direct Interactions with Putative Repair Proteins Links Apoptotic Signaling to CaInternational journal of molecular sciences · 2023Article
- Redefining the architecture of ferlin proteins: Insights into multi-domain protein structure and function.PloS one · 2022Article
- Cell Membrane Repair Assay Using a Two-photon Laser Microscope.Journal of visualized experiments : JoVE · 2018Article
- Dysferlin Gene Mutation Spectrum in a Large Cohort of Chinese Patients with Dysferlinopathy.Chinese medical journal · 2016Article
- Dysferlin Binds SNAREs (Soluble N-Ethylmaleimide-sensitive Factor (NSF) Attachment Protein Receptors) and Stimulates Membrane Fusion in a Calcium-sensitive Manner.The Journal of biological chemistry · 2016Article
- Dysferlinopathy Fibroblasts Are Defective in Plasma Membrane Repair.PLoS currents · 2015Article
- Exon 32 Skipping of Dysferlin Rescues Membrane Repair in Patients' Cells.Journal of neuromuscular diseases · 2015Article
- The Classification, Natural History and Treatment of the Limb Girdle Muscular Dystrophies.Journal of neuromuscular diseases · 2015Article
- A novel dysferlin mutant pseudoexon bypassed with antisense oligonucleotides.Annals of clinical and translational neurology · 2014Article
- Rapid actin-cytoskeleton-dependent recruitment of plasma membrane-derived dysferlin at wounds is critical for muscle membrane repair.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2014Article
- Dysferlin at transverse tubules regulates Ca(2+) homeostasis in skeletal muscle.Frontiers in physiology · 2014Review
- Dysferlin stabilizes stress-induced Ca2+ signaling in the transverse tubule membrane.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
Corrections and comments
- Retraction · 2017-07-28Duplication of/in Image · Falsification/Fabrication of Data · Investigation by Company/Institution ·
- Retracted
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dysferlin is a large transmembrane protein composed of a C-terminal transmembrane domain, two DysF domains, and seven C2 domains that mediate lipid- and protein-binding interactions. Recessive loss-of-function mutations in dysferlin lead to muscular dystrophies, for which no treatment is currently available. The large size of dysferlin precludes its encapsulation into an adeno-associated virus (AAV), the vector of choice for gene delivery to muscle. To design mini-dysferlin molecules suitable for AAV-mediated gene transfer, we tested internally truncated dysferlin constructs, each lacking one of the seven C2 domains, for their ability to localize to the plasma membrane and to repair laser-induced plasmalemmal wounds in dysferlin-deficient human myoblasts. We demonstrate that the dysferlin C2B, C2C, C2D, and C2E domains are dispensable for correct plasmalemmal localization. Furthermore, we show that the C2B, C2C, and C2E domains and, to a lesser extent, the C2D domain are dispensable for dysferlin membrane repair function. On the basis of these results, we designed small dysferlin molecules that can localize to the plasma membrane and reseal laser-induced plasmalemmal injuries and that are small enough to be incorporated into AAV. These results lay the groundwork for AAV-mediated gene therapy experiments in dysferlin-deficient mouse models.
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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.