ArticleThe Journal of biological chemistry2010
Reduced plasma membrane expression of dysferlin mutants is attributed to accelerated endocytosis via a syntaxin-4-associated pathway.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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
26 citing papers in PubMed, 66 citations in OpenAlex.
- Cryo-EM structures of the membrane repair protein dysferlin.Nature communications · 2024Article
- Comprehensive Proteomic Analysis of Dysferlinopathy Unveiling Molecular Mechanisms and Biomarkers Linked to Pathological Progression.CNS neuroscience & therapeutics · 2024Article
- Analysis of Dysferlin Direct Interactions with Putative Repair Proteins Links Apoptotic Signaling to CaInternational journal of molecular sciences · 2023Article
- Minimal expression of dysferlin prevents development of dysferlinopathy in dysferlin exon 40a knockout mice.Acta neuropathologica communications · 2023Article
- Otoferlin as a multirole CaFrontiers in cellular neuroscience · 2023Review
- Angiopoietin2-mediated caveolin1 phosphorylation regulating transcytosis of renal tubular epithelial cell contributes to the occurrence of albuminuria under high glucose exposure.Journal of translational medicine · 2022Article
- 4-Phenylbutyrate restores localization and membrane repair to human dysferlin mutations.iScience · 2022Article
- Functions of Vertebrate Ferlins.Cells · 2020Review
- DNA-Mediated Gene Therapy in a Mouse Model of Limb Girdle Muscular Dystrophy 2B.Molecular therapy. Methods & clinical development · 2017Article
- Limited proteolysis as a tool to probe the tertiary conformation of dysferlin and structural consequences of patient missense variant L344P.The Journal of biological chemistry · 2017Article
- Treatment with Recombinant Human MG53 Protein Increases Membrane Integrity in a Mouse Model of Limb Girdle Muscular Dystrophy 2B.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Article
- Coupling of excitation to CaThe Journal of physiology · 2017Article
- Muscle cell communication in development and repair.Current opinion in pharmacology · 2017Review
- 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
- Plasma Membrane Repair: A Central Process for Maintaining Cellular Homeostasis.Physiology (Bethesda, Md.) · 2015Review
- Membrane Repair: Mechanisms and Pathophysiology.Physiological reviews · 2015Review
- GRAF1 deficiency blunts sarcolemmal injury repair and exacerbates cardiac and skeletal muscle pathology in dystrophin-deficient mice.Skeletal muscle · 2015Article
- GRAF1 promotes ferlin-dependent myoblast fusion.Developmental biology · 2014Article
- Quantitation of the calcium and membrane binding properties of the C2 domains of dysferlin.Biophysical journal · 2014Article
- Alternate splicing of dysferlin C2A confers Ca²⁺-dependent and Ca²⁺-independent binding for membrane repair.Structure (London, England : 1993) · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ferlins are an ancient family of C2 domain-containing proteins, with emerging roles in vesicular trafficking and human disease. Dysferlin mutations cause inherited muscular dystrophy, and dysferlin also shows abnormal plasma membrane expression in other forms of muscular dystrophy. We establish dysferlin as a short-lived (protein half-life approximately 4-6 h) and transitory transmembrane protein (plasma membrane half-life approximately 3 h), with a propensity for rapid endocytosis when mutated, and an association with a syntaxin-4 endocytic route. Dysferlin plasma membrane expression and endocytic rate is regulated by the C2B-FerI-C2C motif, with a critical role identified for C2C. Disruption of C2C dramatically reduces plasma membrane dysferlin (by 2.5-fold), due largely to accelerated endocytosis (by 2.5-fold). These properties of reduced efficiency of plasma membrane expression due to accelerated endocytosis are also a feature of patient missense mutant L344P (within FerI, adjacent to C2C). Importantly, dysferlin mutants that demonstrate accelerated endocytosis also display increased protein lability via endosomal proteolysis, implicating endosomal-mediated proteolytic degradation as a novel basis for dysferlin-deficiency in patients with single missense mutations. Vesicular labeling studies establish that dysferlin mutants rapidly transit from EEA1-positive early endosomes through to dextran-positive lysosomes, co-labeled by syntaxin-4 at multiple stages of endosomal transit. In summary, our studies define a transient biology for dysferlin, relevant to emerging patient therapeutics targeting dysferlin replacement. We introduce accelerated endosomal-directed degradation as a basis for lability of dysferlin missense mutants in dysferlinopathy, and show that dysferlin and syntaxin-4 similarly transit a common endosomal pathway in skeletal muscle cells.
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.