ArticleHuman molecular genetics2011
Pathogenity of some limb girdle muscular dystrophy mutations can result from reduced anchorage to myofibrils and altered stability of calpain 3.
Article in Human molecular genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 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
27 citing papers in PubMed, 47 citations in OpenAlex.
- CaMKIIβ Signaling drives expression of metabolic and stress response genes in skeletal muscle, and its loss contributes to the LGMDR1 phenotype.Human molecular genetics · 2026Article
- Oligomer-dependent and oligomer-independent pathogenesis of muscular dystrophy-associated mutations within the penta-EF-hand domain of calpain-3.The Journal of biological chemistry · 2026Article
- Dominantly inherited muscle disorders: understanding their complexity and exploring therapeutic approaches.Disease models & mechanisms · 2024Review
- Loss of Calpain 3 dysregulates store-operated calcium entry and its exercise response in mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Identification and functional characterization of a novel heterozygous splice‑site mutation in the calpain 3 gene causes rare autosomal dominant limb‑girdle muscular dystrophy.Experimental and therapeutic medicine · 2024Article
- Article
- Loss of calpain 3 dysregulates store-operated calcium entry and its exercise response in mice.bioRxiv : the preprint server for biology · 2024Article
- Case report: A single novel calpain 3 gene variant associated with mild myopathy.Frontiers in genetics · 2024Article
- Degradative Signaling in ATG7-Deficient Skeletal Muscle Following Cardiotoxin Injury.Muscles (Basel, Switzerland) · 2023Article
- Targeting the Ubiquitin-Proteasome System in Limb-Girdle Muscular Dystrophy With CAPN3 Mutations.Frontiers in cell and developmental biology · 2022Article
- CAPN3: A muscle‑specific calpain with an important role in the pathogenesis of diseases (Review).International journal of molecular medicine · 2021Review
- Molecular and cellular basis of genetically inherited skeletal muscle disorders.Nature reviews. Molecular cell biology · 2021Review
- Systemic delivery of AAVrh74.tMCK.hCAPN3 rescues the phenotype in a mouse model for LGMD2A/R1.Molecular therapy. Methods & clinical development · 2021Article
- A Small-Molecule Approach to Restore a Slow-Oxidative Phenotype and Defective CaMKIIβ Signaling in Limb Girdle Muscular Dystrophy.Cell reports. Medicine · 2020Article
- Genetic, Inflammatory, and Epithelial Cell Differentiation Factors Control Expression of Human Calpain-14.G3 (Bethesda, Md.) · 2019Article
- A novel CAPN3 mutation in late-onset limb-girdle muscular dystrophy with early respiratory insufficiency.Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia · 2018Article
- Impaired regeneration in calpain-3 null muscle is associated with perturbations in mTORC1 signaling and defective mitochondrial biogenesis.Skeletal muscle · 2017Article
- Calpain research for drug discovery: challenges and potential.Nature reviews. Drug discovery · 2016Review
- Failure to up-regulate transcription of genes necessary for muscle adaptation underlies limb girdle muscular dystrophy 2A (calpainopathy).Human molecular genetics · 2016Article
- The integrin-adhesome is required to maintain muscle structure, mitochondrial ATP production, and movement forces in Caenorhabditis elegans.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2015Article
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 1 institution in 1 country.
Funding
Abstract
Calpain 3 (CAPN3) is a muscle-specific, calcium-dependent proteinase that is mutated in Limb Girdle Muscle Dystrophy type 2A. Most pathogenic missense mutations in LGMD2A affect CAPN3's proteolytic activity; however, two mutations, D705G and R448H, retain activity but nevertheless cause muscular dystrophy. Previously, we showed that D705G and R448H mutations reduce CAPN3s ability to bind to titin in vitro. In this investigation, we tested the consequence of loss of titin binding in vivo and examined whether this loss can be an underlying pathogenic mechanism in LGMD2A. To address this question, we created transgenic mice that express R448H or D705G in muscles, on wild-type (WT) CAPN3 or knock-out background. Both mutants were readily expressed in insect cells, but when D705G was expressed in skeletal muscle, it was not stable enough to study. Moreover, the D705G mutation had a dominant negative effect on endogenous CAPN3 when expressed on a WT background. The R448H protein was stably expressed in muscles; however, it was more rapidly degraded in muscle extracts compared with WT CAPN3. Increased degradation of R448H was due to non-cysteine, cellular proteases acting on the autolytic sites of CAPN3, rather than autolysis. Fractionation experiments revealed a significant decrease of R448H from the myofibrillar fraction, likely due to the mutant's inability to bind titin. Our data suggest that R448H and D705G mutations affect both CAPN3s anchorage to titin and its stability. These studies reveal a novel mechanism by which mutations that spare enzymatic activity can still lead to calpainopathy.
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.