ArticleCellular and molecular life sciences : CMLS2012
Functional characterization of the human α-cardiac actin mutations Y166C and M305L involved in hypertrophic cardiomyopathy.
Article in Cellular and molecular life sciences : CMLS, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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36 citing papers in PubMed, 62 citations in OpenAlex.
- Two Novel ACTC1 Variants Cause Arthrogryposis Multiplex Congenita.Clinical genetics · 2026Article
- Molecular mechanisms of hotspot variants in cytoskeletal β-actin associated with Baraitser-Winter syndrome.The FEBS journal · 2025Article
- Identification of actin mutants with neurodegenerative disease-like phenotypes via mutagenesis of the actin-ATP interface.Frontiers in cellular neuroscience · 2025Article
- Biochemical characterization of cardiac α-actin mutations A21V and D26N implicated in hypertrophic cardiomyopathy.Cytoskeleton (Hoboken, N.J.) · 2024Article
- Cryo-EM structures of cardiac muscle α-actin mutants M305L and A331P give insights into the structural mechanisms of hypertrophic cardiomyopathy.European journal of cell biology · 2024Article
- High-resolution yeast actin structures indicate the molecular mechanism of actin filament stiffening by cations.Communications chemistry · 2024Article
- Article
- Actin Isoform Composition and Binding Factors Fine-Tune Regulatory Impact of Mical Enzymes.International journal of molecular sciences · 2023Article
- Purification of human β- and γ-actin from budding yeast.Journal of cell science · 2023Article
- Functional Characterization of Cardiac Actin Mutants Causing Hypertrophic (p.A295S) and Dilated Cardiomyopathy (p.R312H and p.E361G).International journal of molecular sciences · 2022Article
- Integration of Cardiac Actin Mutants Causing Hypertrophic (p.A295S) and Dilated Cardiomyopathy (p.R312H and p.E361G) into Cellular Structures.Antioxidants (Basel, Switzerland) · 2021Article
- The origin of the expressed retrotransposed gene ACTBL2 and its influence on human melanoma cells' motility and focal adhesion formation.Scientific reports · 2021Article
- Actin-binding compounds, previously discovered by FRET-based high-throughput screening, differentially affect skeletal and cardiac muscle.The Journal of biological chemistry · 2020Article
- A role for actin flexibility in thin filament-mediated contractile regulation and myopathy.Nature communications · 2020Article
- Actin Mutations and Their Role in Disease.International journal of molecular sciences · 2020Review
- Sexual dimorphism in cardiac transcriptome associated with a troponin C murine model of hypertrophic cardiomyopathy.Physiological reports · 2020Article
- Infantile restrictive cardiomyopathy: cTnI-R170G/W impair the interplay of sarcomeric proteins and the integrity of thin filaments.PloS one · 2020Article
- Thymosin β4 Regulates Focal Adhesion Formation in Human Melanoma Cells and Affects Their Migration and Invasion.Frontiers in cell and developmental biology · 2019Article
- Mutations inF1000Research · 2019Article
- Microtubule associated protein 4 phosphorylation leads to pathological cardiac remodeling in mice.EBioMedicine · 2018Article
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Authors and funding
11 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inherited cardiomyopathies are caused by point mutations in sarcomeric gene products, including α-cardiac muscle actin (ACTC1). We examined the biochemical and cell biological properties of the α-cardiac actin mutations Y166C and M305L identified in hypertrophic cardiomyopathy (HCM). Untagged wild-type (WT) cardiac actin, and the Y166C and M305L mutants were expressed by the baculovirus/Sf9-cell system and affinity purified by immobilized gelsolin G4-6. Their correct folding was verified by a number of assays. The mutant actins also displayed a disturbed intrinsic ATPase activity and an altered polymerization behavior in the presence of tropomyosin, gelsolin, and Arp2/3 complex. Both mutants stimulated the cardiac β-myosin ATPase to only 50 % of WT cardiac F-actin. Copolymers of WT and increasing amounts of the mutant actins led to a reduced stimulation of the myosin ATPase. Transfection of established cell lines revealed incorporation of EGFP- and hemagglutinin (HA)-tagged WT and both mutant actins into cytoplasmic stress fibers. Adenoviral vectors of HA-tagged WT and Y166C actin were successfully used to infect adult and neonatal rat cardiomyocytes (NRCs). The expressed HA-tagged actins were incorporated into the minus-ends of NRC thin filaments, demonstrating the ability to form hybrid thin filaments with endogenous actin. In NRCs, the Y166C mutant led after 72 h to a shortening of the sarcomere length when compared to NRCs infected with WT actin. Thus our data demonstrate that a mutant actin can be integrated into cardiomyocyte thin filaments and by its reduced mode of myosin interaction might be the basis for the initiation of HCM.
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