ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2008
Role of the acidic N' region of cardiac troponin I in regulating myocardial function.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 27 citations in OpenAlex.
- Proteomics of the heart.Physiological reviews · 2024Review
- Cardiac troponin structure-function and the influence of hypertrophic cardiomyopathy associated mutations on modulation of contractility.Archives of biochemistry and biophysics · 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
- Troponin I Mutations R146G and R21C Alter Cardiac Troponin Function, Contractile Properties, and Modulation by Protein Kinase A (PKA)-mediated Phosphorylation.The Journal of biological chemistry · 2015Article
- Effects of HCM cTnI mutation R145G on troponin structure and modulation by PKA phosphorylation elucidated by molecular dynamics simulations.Biophysical journal · 2015Article
- Targeted Next-Generation Sequencing Reveals Hot Spots and Doubly Heterozygous Mutations in Chinese Patients with Familial Cardiomyopathy.BioMed research international · 2015Article
- Cardiac troponin I tyrosine 26 phosphorylation decreases myofilament Ca2+ sensitivity and accelerates deactivation.Journal of molecular and cellular cardiology · 2014Article
- Computational studies of the effect of the S23D/S24D troponin I mutation on cardiac troponin structural dynamics.Biophysical journal · 2014Article
- Cell biology of sarcomeric protein engineering: disease modeling and therapeutic potential.Anatomical record (Hoboken, N.J. : 2007) · 2014Review
- Structural basis for the in situ Ca(2+) sensitization of cardiac troponin C by positive feedback from force-generating myosin cross-bridges.Archives of biochemistry and biophysics · 2013Article
- New insights into the functional significance of the acidic region of the unique N-terminal extension of cardiac troponin I.Biochimica et biophysica acta · 2013Article
- TNNI3K is a novel mediator of myofilament function and phosphorylates cardiac troponin I.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2013Article
- Integration of troponin I phosphorylation with cardiac regulatory networks.Circulation research · 2013Review
- N-terminal phosphorylation of cardiac troponin-I reduces length-dependent calcium sensitivity of contraction in cardiac muscle.The Journal of physiology · 2013Article
- Significance of troponin dynamics for Ca2+-mediated regulation of contraction and inherited cardiomyopathy.The Journal of biological chemistry · 2012Article
- 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
- Protein phosphorylation and signal transduction in cardiac thin filaments.The Journal of biological chemistry · 2011Review
- Signaling and myosin-binding protein C.The Journal of biological chemistry · 2011Review
- Removal of the cardiac troponin I N-terminal extension improves cardiac function in aged mice.The Journal of biological chemistry · 2010Article
- Phosphorylation of cardiac troponin I at protein kinase C site threonine 144 depresses cooperative activation of thin filaments.The Journal of biological chemistry · 2010Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Cardiac troponin I (cTnI) phosphorylation modulates myocardial contractility and relaxation during beta-adrenergic stimulation. cTnI differs from the skeletal isoform in that it has a cardiac specific N' extension of 32 residues (N' extension). The role of the acidic N' region in modulating cardiac contractility has not been fully defined. To test the hypothesis that the acidic N' region of cTnI helps regulate myocardial function, we generated cardiac-specific transgenic mice in which residues 2-11 (cTnI(Delta2-11)) were deleted. The hearts displayed significantly decreased contraction and relaxation under basal and beta-adrenergic stress compared to nontransgenic hearts, with a reduction in maximal Ca(2+)-dependent force and maximal Ca(2+)-activated Mg(2+)-ATPase activity. However, Ca(2+) sensitivity of force development and cTnI-Ser(23/24) phosphorylation were not affected. Chemical shift mapping shows that both cTnI and cTnI(Delta2-11) interact with the N lobe of cardiac troponin C (cTnC) and that phosphorylation at Ser(23/24) weakens these interactions. These observations suggest that residues 2-11 of cTnI, comprising the acidic N' region, do not play a direct role in the calcium-induced transition in the cardiac regulatory or N lobe of cTnC. We hypothesized that phosphorylation at Ser(23/24) induces a large conformational change positioning the conserved acidic N region to compete with actin for the inhibitory region of cTnI. Consistent with this hypothesis, deletion of the conserved acidic N' region results in a decrease in myocardial contractility in the cTnI(Delta2-11) mice demonstrating the importance of acidic N' region in regulating myocardial contractility and mediating the response of the heart to beta-AR stimulation.
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