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Titin and Titin-Associated Proteins in Myocardial Stress-Sensing and Mechanical Dysfunction

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Book cover Mechanosensitivity of the Heart

Part of the book series: Mechanosensitivity in Cells and Tissues ((MECT,volume 3))

Abstract

Mechanical stress signals transmitted through the heart walls during hemodynamic loading are sensed by the myocytes. These signals play an important role in physiological heart development and hypertrophy, but disruption of the well-balanced stress-sensing machinery causes mechanical dysregulation, cardiac remodelling, and heart failure. In cardiomyocytes, nodal points of force transmission and mechanosensing reside in the Z-disk, M-band, and I-band regions of the sarcomeres. Longitudinal linkage of these regions is provided by the titin filament and several “hot spots” along this giant protein may be, along with some of its > 20 ligands, pivotal to the myofibrillar stretch response. This review outlines the known interaction partners of titin and highlights the putative stress/stretch sensor complexes at titin’s NH2 and COOH termini and their role in myopathies. Another focus is the elastic I-band titin section, which interacts with a diverse number of proteins and whose main function is as a determinant of diastolic distensibility and passive stiffness. The discussion summarizes recent insights into the plasticity, mechanical role, and regulation of the elastic titin springs in cardiac development and human heart disease. Titin and titin-based protein complexes are now recognized as integral parts of the mechanosensitive protein network and as critical components in cardiomyocyte stress/stretch signalling.

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Acknowledgements

I would like to thank the Deutsche Forschungsgemeinschaft for financial support.

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  1. Physiology and Biophysics Unit, University of Muenster, Muenster, Germany

    Wolfgang A. Linke

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  1. Dept. Fundamental &, Russian State Medical University, Ostrovitjanova Str. 1, Moskva, 117997, Russian Federation

    Andre Kamkin

  2. Dept. Fundamental &, Russian State Medical University, Ostrovitjanova Str. 1, Moskva, 117997, Russian Federation

    Irina Kiseleva

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Linke, W.A. (2009). Titin and Titin-Associated Proteins in Myocardial Stress-Sensing and Mechanical Dysfunction. In: Kamkin, A., Kiseleva, I. (eds) Mechanosensitivity of the Heart. Mechanosensitivity in Cells and Tissues, vol 3. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-2850-1_1

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