ArticleHuman molecular genetics2012
Impaired calcium calmodulin kinase signaling and muscle adaptation response in the absence of calpain 3.
Article in Human molecular genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 46 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
- Calpainopathy (limb-girdle muscular dystrophy type R1): clinical features, diagnostic approaches, and biotechnological treatment methods.Journal of neuromuscular diseases · 2025Review
- 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
- Article
- Loss of calpain 3 dysregulates store-operated calcium entry and its exercise response in mice.bioRxiv : the preprint server for biology · 2024Article
- A retrospective study on the clinical and molecular outcomes of calpainopathy in a Turkish patient cohort.Turkish journal of medical sciences · 2024Article
- Cas9-induced single cut enables highly efficient and template-free repair of a muscular dystrophy causing founder mutation.Molecular therapy. Nucleic acids · 2023Article
- Novel mutations in theFrontiers in genetics · 2023Article
- Targeting the Ubiquitin-Proteasome System in Limb-Girdle Muscular Dystrophy With CAPN3 Mutations.Frontiers in cell and developmental biology · 2022Article
- Short-term step reduction reduces citrate synthase activity without altering skeletal muscle markers of oxidative metabolism or insulin-mediated signaling in young males.Journal of applied physiology (Bethesda, Md. : 1985) · 2021Article
- Molecular and cellular basis of genetically inherited skeletal muscle disorders.Nature reviews. Molecular cell biology · 2021Review
- CAPN3: A muscle‑specific calpain with an important role in the pathogenesis of diseases (Review).International journal of molecular medicine · 2021Review
- Systemic delivery of AAVrh74.tMCK.hCAPN3 rescues the phenotype in a mouse model for LGMD2A/R1.Molecular therapy. Methods & clinical development · 2021Article
- Current and Future Therapeutic Strategies for Limb Girdle Muscular Dystrophy Type R1: Clinical and Experimental Approaches.Pathophysiology : the official journal of the International Society for Pathophysiology · 2021Review
- A Small-Molecule Approach to Restore a Slow-Oxidative Phenotype and Defective CaMKIIβ Signaling in Limb Girdle Muscular Dystrophy.Cell reports. Medicine · 2020Article
- The ties that bind: functional clusters in limb-girdle muscular dystrophy.Skeletal muscle · 2020Review
- Calcium Mechanisms in Limb-Girdle Muscular Dystrophy withInternational journal of molecular sciences · 2019Review
- Calpain 3 and CaMKIIβ signaling are required to induce HSP70 necessary for adaptive muscle growth after atrophy.Human molecular genetics · 2018Article
- Failure to up-regulate transcription of genes necessary for muscle adaptation underlies limb girdle muscular dystrophy 2A (calpainopathy).Human molecular genetics · 2016Article
- Calpain 3 deficiency affects SERCA expression and function in the skeletal muscle.Expert reviews in molecular medicine · 2016Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Mutations in the non-lysosomal, cysteine protease calpain 3 (CAPN3) result in the disease limb girdle muscular dystrophy type 2A (LGMD2A). CAPN3 is localized to several subcellular compartments, including triads, where it plays a structural, rather than a proteolytic, role. In the absence of CAPN3, several triad components are reduced, including the major Ca(2+) release channel, ryanodine receptor (RyR). Furthermore, Ca(2+) release upon excitation is impaired in the absence of CAPN3. In the present study, we show that Ca-calmodulin protein kinase II (CaMKII) signaling is compromised in CAPN3 knockout (C3KO) mice. The CaMK pathway has been previously implicated in promoting the slow skeletal muscle phenotype. As expected, the decrease in CaMKII signaling that was observed in the absence of CAPN3 is associated with a reduction in the slow versus fast muscle fiber phenotype. We show that muscles of WT mice subjected to exercise training activate the CaMKII signaling pathway and increase expression of the slow form of myosin; however, muscles of C3KO mice do not exhibit these adaptive changes to exercise. These data strongly suggest that skeletal muscle's adaptive response to functional demand is compromised in the absence of CAPN3. In agreement with our mouse studies, RyR levels were also decreased in biopsies from LGMD2A patients. Moreover, we observed a preferential pathological involvement of slow fibers in LGMD2A biopsies. Thus, impaired CaMKII signaling and, as a result, a weakened muscle adaptation response identify a novel mechanism that may underlie LGMD2A and suggest a pharmacological target that should be explored for therapy.
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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.