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

Biophysics Reviews
Nazha HamdaniWolfgang A Linke

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 hear...Continue Reading

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Citations

Dec 7, 2018·Journal of Applied Physiology·Johanna K Freundt, Wolfgang A Linke
Oct 26, 2018·Journal of Applied Physiology·Gary F Mitchell
Mar 29, 2019·Pflügers Archiv : European journal of physiology·Dalma KellermayerHenk Granzier
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Nov 1, 2018·Physiological Reviews·Jolanda van der Velden, Ger J M Stienen
Jan 10, 2020·Journal of Muscle Research and Cell Motility·Lisa D GlassBrian R MacIntosh
Jan 21, 2021·Experimental Biology and Medicine·Lisa Kobos, Jonathan Shannahan
Mar 16, 2021·Frontiers in Cell and Developmental Biology·Juliane Münch, Salim Abdelilah-Seyfried
Dec 15, 2020·Journal of Human Kinetics·Agnieszka Maciejewska-SkrendoMarek Sawczuk
Feb 28, 2021·Annual Review of Biophysics·Joseph D PowersThomas L Daniel
Jun 26, 2021·Frontiers in Molecular Biosciences·Arthur ForerMichael W Berns
Jul 25, 2021·International Journal of Molecular Sciences·Adeleye O Adewale, Young-Hoon Ahn
Aug 15, 2021·Biophysical Journal·Neil Ibata, Eugene M Terentjev

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Methods Mentioned

BETA
atomic force microscopy
transgenic
AFM
biopsies

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