The Journal of Physiological Sciences
Online ISSN : 1880-6562
Print ISSN : 1880-6546
Review
Physiological Functions of the Giant Elastic Protein Titin in Mammalian Striated Muscle
Norio FukudaHenk L. GranzierShin'ichi IshiwataSatoshi Kurihara
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2008 Volume 58 Issue 3 Pages 151-159

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Abstract

The striated muscle sarcomere contains the third filament comprising the giant elastic protein titin, in addition to thick and thin filaments. Titin is the primary source of nonactomyosin-based passive force in both skeletal and cardiac muscles, within the physiological sarcomere length range. Titin's force repositions the thick filaments in the center of the sarcomere after contraction or stretch and thus maintains sarcomere length and structural integrity. In the heart, titin determines myocardial wall stiffness, thereby regulating ventricular filling. Recent studies have revealed the mechanisms involved in the fine tuning of titin-based passive force via alternative splicing or posttranslational modification. It has also been discovered that titin performs roles that go beyond passive force generation, such as a regulation of the Frank-Starling mechanism of the heart. In this review, we discuss how titin regulates passive and active properties of striated muscle during normal muscle function and during disease.

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© 2008 by The Physiological Society of Japan
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