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Hamdani N, Herwig M, Linke WA. Tampering with springs: phosphorylation of titin affecting the mechanical function of cardiomyocytes. Biophys Rev. 2017;9(3):225-237doi: 10.1007/s12551-017-0263-9.
Hamdani, N., Herwig, M., & Linke, W. A. (2017). Tampering with springs: phosphorylation of titin affecting the mechanical function of cardiomyocytes. Biophysical reviews, 9(3), 225-237. https://doi.org/10.1007/s12551-017-0263-9
Hamdani, Nazha, et al. "Tampering with springs: phosphorylation of titin affecting the mechanical function of cardiomyocytes." Biophysical reviews vol. 9,3 (2017): 225-237. doi: https://doi.org/10.1007/s12551-017-0263-9
Hamdani N, Herwig M, Linke WA. Tampering with springs: phosphorylation of titin affecting the mechanical function of cardiomyocytes. Biophys Rev. 2017 Jun;9(3):225-237. doi: 10.1007/s12551-017-0263-9. Epub 2017 Apr 10. PMID: 28510118; PMCID: PMC5498327.
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Biophys Rev. 2017 Jun;9(3):225-237. doi: 10.1007/s12551-017-0263-9. Epub 2017 Apr 10.

Tampering with springs: phosphorylation of titin affecting the mechanical function of cardiomyocytes.

Biophysical reviews

Nazha Hamdani, Melissa Herwig, Wolfgang A Linke

Affiliations

  1. Department of Cardiovascular Physiology, Ruhr University Bochum, MA 03/56, 44780, Bochum, Germany.
  2. Department of Cardiovascular Physiology, Ruhr University Bochum, MA 03/56, 44780, Bochum, Germany. [email protected].
  3. Deutsches Zentrum für Herz-Kreislaufforschung, Partner Site Göttingen, Göttingen, Germany. [email protected].
  4. Cardiac Mechanotransduction Group, Clinic for Cardiology and Pneumology, University Medical Center, Göttingen, Germany. [email protected].

PMID: 28510118 PMCID: PMC5498327 DOI: 10.1007/s12551-017-0263-9

Abstract

Reversible post-translational modifications of various cardiac proteins regulate the mechanical properties of the cardiomyocytes and thus modulate the contractile performance of the heart. The giant protein titin forms a continuous filament network in the sarcomeres of striated muscle cells, where it determines passive tension development and modulates active contraction. These mechanical properties of titin are altered through post-translational modifications, particularly phosphorylation. Titin contains hundreds of potential phosphorylation sites, the functional relevance of which is only beginning to emerge. Here, we provide a state-of-the-art summary of the phosphorylation sites in titin, with a particular focus on the elastic titin spring segment. We discuss how phosphorylation at specific amino acids can reduce or increase the stretch-induced spring force of titin, depending on where the spring region is phosphorylated. We also review which protein kinases phosphorylate titin and how this phosphorylation affects titin-based passive tension in cardiomyocytes. A comprehensive overview is provided of studies that have measured altered titin phosphorylation and titin-based passive tension in myocardial samples from human heart failure patients and animal models of heart disease. As our understanding of the broader implications of phosphorylation in titin progresses, this knowledge could be used to design targeted interventions aimed at reducing pathologically increased titin stiffness in patients with stiff hearts.

Keywords: Cardiomyocytes; Diastolic function; Heart failure; Muscle cell mechanics; Posttranslational modification; Stiffness

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