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First published online on March 28, 2002.
 Copyright © 2002 by The Physiological Society
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Received November 21, 2001
Accepted after revision February 26, 2002

Cardiac titin: an adjustable multi-functional spring

H. Granzier1* and Siegfried Labeit2

1 Department VCAPP, Washington State University, Pullman, WA 99164-6520, USA
2 Institut für Anästhesiologie und Operative Intensivmedizin, Universitätsklinikum, Theodor-Kutzer-Ufer, 68167 Mannheim, Germany

* To whom correspondence should be addressed. E-mail: granzier{at}wsunix.wsu.edu.

The giant elastic protein titin contains a molecular spring segment that underlies the majority of myocardial passive stiffness. The mechanical characteristics of this spring may be tuned to match changing mechanical demands placed on muscle, using mechanisms that operate on different time scales and that include post-transcriptional and post-translational processes. Recent work also suggests that titin performs roles that go beyond passive stiffness generation. In contracting myocardium, titin may modulate actomyosin interaction by a titin-based alteration of the distance between myosin heads and actin. Furthermore, novel ligands have been identified that link titin to membrane channels, protein turnover and gene expression. This review highlights that titin is a versatile and adjustable spring with a range of important functions in passive and contracting myocardium.




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