ArticleJCI insight2019
Cullin-3 dependent deregulation of ACTN1 represents a new pathogenic mechanism in nemaline myopathy.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 25 citations in OpenAlex.
- USP14-mediated stabilization of ACTN1 maintains mesenchymal characteristics in glioblastoma.Communications biology · 2025Article
- Comparative Transcriptomic Analysis Between High- and Low-Growth-Rate Meat-Type Rabbits Reveals Key Pathways Associated with Muscle Development.Animals : an open access journal from MDPI · 2025Article
- Neddylation drives myofibrillogenesis in the developing heart.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Exploring Gene Expression and Alternative Splicing in Duck Embryonic Myoblasts via Full-Length Transcriptome Sequencing.Veterinary sciences · 2024Article
- Muscle Proteome Analysis of Facioscapulohumeral Dystrophy Patients Reveals a Metabolic Rewiring Promoting Oxidative/Reductive Stress Contributing to the Loss of Muscle Function.Antioxidants (Basel, Switzerland) · 2024Article
- ACTN1 promotes HNSCC tumorigenesis and cisplatin resistance by enhancing MYH9-dependent degradation of GSK-3β and integrin β1-mediated phosphorylation of FAK.Journal of experimental & clinical cancer research : CR · 2023Article
- Clinico-pathological features and mutational spectrum of 16 nemaline myopathy patients from a Chinese neuromuscular center.Acta neurologica Belgica · 2022Article
- Ubiquitin ligases: guardians of mammalian development.Nature reviews. Molecular cell biology · 2022Review
- Genomic Analyses of Unveil Helmeted Guinea Fowl (Numida meleagris) Domestication in West Africa.Genome biology and evolution · 2021Article
- Transcriptome profiling analysis of muscle tissue reveals potential candidate genes affecting water holding capacity in Chinese Simmental beef cattle.Scientific reports · 2021Article
- A novel and recurrent KLHL40 pathogenic variants in a Chinese family of multiple affected neonates with nemaline myopathy 8.Molecular genetics & genomic medicine · 2021Article
- Epigenetics of Muscle- and Brain-Specific Expression of KLHL Family Genes.International journal of molecular sciences · 2020Article
- The Role of Cullin-RING Ligases in Striated Muscle Development, Function, and Disease.International journal of molecular sciences · 2020Review
- The Ubiquitin Proteasome System in Neuromuscular Disorders: Moving Beyond Movement.International journal of molecular sciences · 2020Review
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Authors and funding
9 authors at 5 institutions in 4 countries.
Funding
Abstract
Nemaline myopathy is a congenital neuromuscular disorder characterized by muscle weakness, fiber atrophy and presence of nemaline bodies within myofibers. However, the understanding of underlying pathomechanisms is lacking. Recently, mutations in KBTBD13, KLHL40 and KLHL41, three substrate adaptors for the E3-ubiquitin ligase Cullin-3, have been associated with early-onset nemaline myopathies. We hypothesized that deregulation of Cullin-3 and its muscle protein substrates may be responsible for the disease development. Using Cullin-3 knockout mice, we identified accumulation of non-muscle alpha-Actinins (ACTN1 and ACTN4) in muscles of these mice, which we also observed in KBTBD13 patients. Our data reveal that proper regulation of Cullin-3 activity and ACTN1 levels is essential for normal muscle and neuromuscular junction development. While ACTN1 is naturally downregulated during myogenesis, its overexpression in C2C12 myoblasts triggered defects in fusion, myogenesis and acetylcholine receptor clustering; features that we characterized in Cullin-3 deficient mice. Taken together, our data highlight the importance for Cullin-3 mediated degradation of ACTN1 for muscle development, and indicate a new pathomechanism for the etiology of myopathies seen in Cullin-3 knockout mice and nemaline myopathy patients.
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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.