ArticleeLife2017
KLHL41 stabilizes skeletal muscle sarcomeres by nonproteolytic ubiquitination.
Article in eLife, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed.
- Klhl41b orchestrates sarcomere assembly and growth to drive skeletal muscle hypertrophy in vivo.Skeletal muscle · 2026Article
- Discovery of a KLHL41 Ligand for Muscle Specific Protein Degradation.Nature communications · 2026Article
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- Plasma Extracellular Vesicles Contain Protein Biomarkers for Capturing Stages of Metabolic Dysfunction-Associated Steatotic Liver Disease: A Preliminary Exploratory Study.Biomolecules · 2025Article
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- A window into intracellular events in myositis through subcellular proteomics.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- An atlas of caspase cleavage events in differentiating muscle cells.Protein science : a publication of the Protein Society · 2024Article
- Review
- Transcriptome-Based Identification of the Muscle Tissue-Specific Expression GeneAnimals : an open access journal from MDPI · 2023Article
- Net39 protects muscle nuclei from mechanical stress during the pathogenesis of Emery-Dreifuss muscular dystrophy.The Journal of clinical investigation · 2023Article
- Molecular signatures of inherited and acquired sporadic late onset nemaline myopathies.Acta neuropathologica communications · 2023Article
- Metabolomics and Proteomics Characterizing Hepatic Reactions to Dietary Linseed Oil in Duck.International journal of molecular sciences · 2022Article
- Article
- Exercise mediates ubiquitin signalling in human skeletal muscle.FASEB bioAdvances · 2022Article
- Defective protein degradation in genetic disorders.Biochimica et biophysica acta. Molecular basis of disease · 2022Review
- Ubiquitin ligases: guardians of mammalian development.Nature reviews. Molecular cell biology · 2022Review
- Integration of RNA-seq and ATAC-seq identifies muscle-regulated hub genes in cattle.Frontiers in veterinary science · 2022Article
- Gill and Liver Transcript Expression Changes Associated With Gill Damage in Atlantic Salmon (Frontiers in immunology · 2022Article
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Authors and funding
7 authors.
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Abstract
Maintenance of muscle function requires assembly of contractile proteins into highly organized sarcomeres. Mutations in Kelch-like protein 41 (KLHL41) cause nemaline myopathy, a fatal muscle disorder associated with sarcomere disarray. We generated KLHL41 mutant mice, which display lethal disruption of sarcomeres and aberrant expression of muscle structural and contractile proteins, mimicking the hallmarks of the human disease. We show that KLHL41 is poly-ubiquitinated and acts, at least in part, by preventing aggregation and degradation of Nebulin, an essential component of the sarcomere. Furthermore, inhibition of KLHL41 poly-ubiquitination prevents its stabilization of nebulin, suggesting a unique role for ubiquitination in protein stabilization. These findings provide new insights into the molecular etiology of nemaline myopathy and reveal a mechanism whereby KLHL41 stabilizes sarcomeres and maintains muscle function by acting as a molecular chaperone. Similar mechanisms for protein stabilization likely contribute to the actions of other Kelch proteins.
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