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.