Structure-function relations of the giant elastic protein titin in striated and smooth muscle cells.
The striated muscle sarcomere contains, in addition to thin and thick filaments, a third myofilament comprised of titin. The extensible region of titin spans the I-band region of the sarcomere and develops passive force in stretched sarcomeres. This force positions the A-bands in the middle of the sarcomere, maintains sarcomere length homogeneity and, importantly, is responsible for myocardial passive tension that determines diastolic filling. Recent work suggests that smooth muscle expresses a truncated titin isoform with a short extensible region that is predicted to develop high passive force levels. Several mechanisms for tuning the titin-based passive tension have been discovered that involve alternative splicing as well as posttranslational modification, mechanisms that are at play both during normal muscle function as well as during disease.
Granzier
Henk
H
Department of Veterinary and Comparative Anatomy, Pharmacology Physiology, and Physiology, Washington State University, Pullman, Washington, USA.
Labeit
Siegfried
S
D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D064211:Connectin; D004548:Elasticity; D006801:Humans; D009119:Muscle Contraction / Q000502:physiology*; D009124:Muscle Proteins / Q000235:genetics / Q000502:physiology*; D009130:Muscle, Smooth / Q000502:physiology* / Q000648:ultrastructure; D054792:Muscle, Striated / Q000502:physiology* / Q000648:ultrastructure; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000648:ultrastructure; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology*; D012518:Sarcomeres / Q000378:metabolism / Q000648:ultrastructure
D064211:Connectin; D009124:Muscle Proteins; D020033:Protein Isoforms; C577285:TTN protein, human; D011494:Protein Kinases