ArticleThe Journal of biological chemistry2010
Mutual rescues between two dominant negative mutations in cardiac troponin I and cardiac troponin T.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 22 citations in OpenAlex.
- Posttranscriptional Regulation by Proteins and Noncoding RNAs.Advances in experimental medicine and biology · 2024Article
- Increases of desmin and α-actinin in mouse cardiac myofibrils as a response to diastolic dysfunction.Journal of molecular and cellular cardiology · 2016Article
- TNNT1, TNNT2, and TNNT3: Isoform genes, regulation, and structure-function relationships.Gene · 2016Review
- Effect of N-Terminal Extension of Cardiac Troponin I on the Ca(2+) Regulation of ATP Binding and ADP Dissociation of Myosin II in Native Cardiac Myofibrils.Biochemistry · 2016Article
- TNNI1, TNNI2 and TNNI3: Evolution, regulation, and protein structure-function relationships.Gene · 2016Review
- Protein Structure-Function Relationship at Work: Learning from Myopathy Mutations of the Slow Skeletal Muscle Isoform of Troponin T.Frontiers in physiology · 2016Review
- Dysferlin deficiency blunts β-adrenergic-dependent lusitropic function of mouse heart.The Journal of physiology · 2015Article
- Cardiac troponin I Pro82Ser variant induces diastolic dysfunction, blunts β-adrenergic response, and impairs myofilament cooperativity.Journal of applied physiology (Bethesda, Md. : 1985) · 2015Article
- Distinct conformational and functional effects of two adjacent pathogenic mutations in cardiac troponin I at the interface with troponin T.FEBS open bio · 2015Article
- Abnormal splicing in the N-terminal variable region of cardiac troponin T impairs systolic function of the heart with preserved Frank-Starling compensation.Physiological reports · 2014Article
- A dominantly negative mutation in cardiac troponin I at the interface with troponin T causes early remodeling in ventricular cardiomyocytes.American journal of physiology. Cell physiology · 2014Article
- Ca(2+)-regulatory function of the inhibitory peptide region of cardiac troponin I is aided by the C-terminus of cardiac troponin T: Effects of familial hypertrophic cardiomyopathy mutations cTnI R145G and cTnT R278C, alone and in combination, on filament sliding.Archives of biochemistry and biophysics · 2014Article
- Gene regulation, alternative splicing, and posttranslational modification of troponin subunits in cardiac development and adaptation: a focused review.Frontiers in physiology · 2014Review
- The Drosophila F-box protein dSkp2 regulates cell proliferation by targeting Dacapo for degradation.Molecular biology of the cell · 2013Article
- Up-regulation of alpha-smooth muscle actin in cardiomyocytes from non-hypertrophic and non-failing transgenic mouse hearts expressing N-terminal truncated cardiac troponin I.FEBS open bio · 2013Article
- The heart-specific NH2-terminal extension regulates the molecular conformation and function of cardiac troponin I.American journal of physiology. Heart and circulatory physiology · 2012Article
- Structure of the NH2-terminal variable region of cardiac troponin T determines its sensitivity to restrictive cleavage in pathophysiological adaptation.Archives of biochemistry and biophysics · 2011Article
- Troponin T isoforms and posttranscriptional modifications: Evolution, regulation and function.Archives of biochemistry and biophysics · 2011Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Troponin T (TnT) and troponin I (TnI) are two evolutionarily and functionally linked subunits of the troponin complex that regulates striated muscle contraction. We previously reported a single amino acid substitution in the highly conserved TnT-binding helix of cardiac TnI (cTnI) in wild turkey hearts in concurrence with an abnormally spliced myopathic cardiac TnT (cTnT) (Biesiadecki, B. J., Schneider, K. L., Yu, Z. B., Chong, S. M., and Jin, J. P. (2004) J. Biol. Chem. 279, 13825-13832). To investigate the functional effect of this cTnI mutation and its potential value in compensating for the cTnT abnormality, we developed transgenic mice expressing the mutant cTnI (K118C) in the heart with or without the deletion of the endogenous cTnI gene to mimic the homozygote and heterozygote of wild turkeys. Double and triple transgenic mice were created by crossing the cTnI-K118C lines with transgenic mice overexpressing the myopathic cTnT (exon 7 deletion). Functional studies of ex vivo working hearts found that cTnI-K118C alone had a dominantly negative effect on diastolic function and blunted the inotropic responses of cardiac muscle to beta-adrenergic stimuli without abolishing the protein kinase A-dependent phosphorylation of cTnI. When co-expressed with the cTnT mutation, cTnI-K118C corrected the significant depression of systolic function caused by cTnT exon 7 deletion, and the co-existence of exon 7-deleted cTnT minimized the diastolic abnormality of cTnI-K118C. Characterization of this naturally selected pair of mutually rescuing mutations demonstrated that TnI-TnT interaction is a critical link in the Ca(2+) signaling and beta-adrenergic regulation in cardiac muscle, suggesting a potential target for the treatment of troponin cardiomyopathies and heart failure.
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