ArticleJournal of neuropathology and experimental neurology2008
Disease severity and thin filament regulation in M9R TPM3 nemaline myopathy.
Article in Journal of neuropathology and experimental neurology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 27 citations in OpenAlex.
- Tropomyosin 3 (TPM3) function in skeletal muscle and in myopathy.Skeletal muscle · 2023Review
- A novel variant in the tropomyosin 3 gene presenting as an adult-onset distal myopathy - a case report.BMC neurology · 2023Article
- Novel Compound Heterozygous Splice-Site Variants in TPM3 Revealed by RNA Sequencing in a Patient with an Unusual Form of Nemaline Myopathy: A Case Report.Journal of neuromuscular diseases · 2023Article
- Impact of Troponin in Cardiomyopathy Development Caused by Mutations in Tropomyosin.International journal of molecular sciences · 2022Article
- Mutual dependence between tropomodulin and tropomyosin in the regulation of sarcomeric actin assembly in Caenorhabditis elegans striated muscle.European journal of cell biology · 2022Article
- M8R tropomyosin mutation disrupts actin binding and filament regulation: The beginning affects the middle and end.The Journal of biological chemistry · 2020Article
- Looking for Targets to Restore the Contractile Function in Congenital Myopathy Caused by GlnInternational journal of molecular sciences · 2020Article
- Muscle weakness in TPM3-myopathy is due to reduced Ca2+-sensitivity and impaired acto-myosin cross-bridge cycling in slow fibres.Human molecular genetics · 2015Article
- Functional effects of mutations in the tropomyosin-binding sites of tropomodulin1 and tropomodulin3.Cytoskeleton (Hoboken, N.J.) · 2014Article
- Differential actin-regulatory activities of Tropomodulin1 and Tropomodulin3 with diverse tropomyosin and actin isoforms.The Journal of biological chemistry · 2014Article
- Article
- Novel deletion of lysine 7 expands the clinical, histopathological and genetic spectrum of TPM2-related myopathies.Brain : a journal of neurology · 2013Article
- Phenotypes of myopathy-related beta-tropomyosin mutants in human and mouse tissue cultures.PloS one · 2013Article
- Tropomodulins: pointed-end capping proteins that regulate actin filament architecture in diverse cell types.Cytoskeleton (Hoboken, N.J.) · 2012Review
- Dynamic regulation of sarcomeric actin filaments in striated muscle.Cytoskeleton (Hoboken, N.J.) · 2010Review
- Tropomodulin isoforms regulate thin filament pointed-end capping and skeletal muscle physiology.The Journal of cell biology · 2010Article
- Mutations of tropomyosin 3 (TPM3) are common and associated with type 1 myofiber hypotrophy in congenital fiber type disproportion.Human mutation · 2010Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
The mechanism of muscle weakness was investigated in an Australian family with an M9R mutation in TPM3 (alpha-tropomyosin(slow)). Detailed protein analyses of 5 muscle samples from 2 patients showed that nemaline bodies are restricted to atrophied Type 1 (slow) fibers in which the TPM3 gene is expressed. Developmental expression studies showed that alpha-tropomyosin(slow) is not expressed at significant levels until after birth, thereby likely explaining the childhood (rather than congenital) disease onset in TPM3 nemaline myopathy. Isoelectric focusing demonstrated that alpha-tropomyosin(slow) dimers, composed of equal ratios of wild-type and M9R-alpha-tropomyosin(slow), are the dominant tropomyosin species in 3 separate muscle groups from an affected patient. These findings suggest that myopathy-related slow fiber predominance likely contributes to the severity of weakness in TPM3 nemaline myopathy because of increased proportions of fibers that express the mutant protein. Using recombinant proteins and far Western blot, we demonstrated a higher affinity of tropomodulin for alpha-tropomyosin(slow) compared with beta-tropomyosin; the M9R substitution within alpha-tropomyosin(slow) greatly reduced this interaction. Finally, transfection of the M9R mutated and wild-type alpha-tropomyosin(slow) into myoblasts revealed reduced incorporation into stress fibers and disruption of the filamentous actin network by the mutant protein. Collectively, these results provide insights into the clinical features and pathogenesis of M9R-TPM3 nemaline myopathy.
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