Circulation Research. 2004;94:284-295
doi: 10.1161/01.RES.0000117769.88862.F8
doi: 10.1161/01.RES.0000117769.88862.F8
© 2004 American Heart Association, Inc.
Reviews |
The Giant Protein Titin
A Major Player in Myocardial Mechanics, Signaling, and Disease
From the Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology (H.L.G.), Washington State University, Pullman, Wash; Abteilung für Anästhesiologie und Operative Intensivmedizin (S.L.), Universitätsklinikum Mannheim, Germany.
Correspondence to Henk L. Granzier, Washington State University, Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Wegner Hall, 205, Pullman, WA 99164. E-mail granzier{at}wsunix.wsu.edu
This Review is part of a thematic series on Myocyte Intra- and Extrasarcomeric Structural Proteins, which includes the following articles:
The Giant Protein Titin: A Major Player in Myocardial Mechanics, Signaling, and Disease
The Dystrophin Glycoprotein Complex: Structure and Function in Cardiac and Skeletal Muscle
Cardiac Myosin Binding Protein C: Its Role in Physiology and Disease
David Kass Editor
The sarcomere contains, in addition to thin and thick filaments, a filament composed of the giant protein titin (also known as connectin). Titin molecules anchor in the Z-disc and extend to the M-line region of the sarcomere. The majority of titin’s I-band region functions as a molecular spring. This spring maintains the precise structural arrangement of thick and thin filaments, and gives rise to passive muscle stiffness; an important determinant of diastolic filling. Earlier work on titin has been reviewed before. In this study, our main focus is on recent findings vis-à-vis titin’s molecular spring segments in cardiac titins, including the discovery of fetal cardiac isoforms with novel spring elements. We also discuss new insights regarding the role of titin as a biomechanical sensor and signaling molecule. We will end with focusing on the rapidly growing knowledge regarding titinopathies.
Key Words: myocardial stiffness • contractility • stretch • connectin • passive stiffness
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