title: A Titan but not necessarily a ruler: assessing the role of titin during thick filament patterning and assembly.
abstract: The sarcomeres of striated muscle are among the most elaborate and dynamic eukaryotic cellular protein machinery, and the mechanisms by which these semicrystalline filament networks are initially patterned and assembled remain contentious. In addition to the acto-myosin filaments that provide motor function, the sarcomere contains titin filaments, comprised of individual molecules of the giant Ig- and fibronectin domain-rich protein titin. Titin is the largest known protein, containing many structurally distinct domains with a variety of proposed functions, including sarcomere stabilization, the prevention of over-stretching, and returning to resting length after contraction. One molecule of titin, which binds to both the Z-disk and the M-line, spans a half-sarcomere, and is proposed to serve as a "molecular ruler" that dictates the spacing of sarcomeres. The semirigid rod-like A-band region of titin has also been proposed to act as a scaffold for thick filament formation during muscle development, but despite decades of research, this hypothesis has not been rigorously tested. Recent studies in zebrafish have brought into question the necessity for the A-band region of titin during the early stages of sarcomere patterning. In this review, we give an overview of the many different roles of titin in the development and function of striated muscle, and address the validity of the "molecular ruler" model of myofibrillogenesis in light of the current literature.
authors.affiliation: Faculty of Dentistry, Department of Oral Health Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: J Layne
authors.initials: JL
authors.lastname: Myhre
authors.forename: David
authors.initials: D
authors.lastname: Pilgrim
mesh_terms: D000818:Animals; D064211:Connectin / Q000378:metabolism*; D006801:Humans; D024510:Muscle Development; D054792:Muscle, Striated / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D012518:Sarcomeres / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D064211:Connectin
keywords: muscle; sarcomere; titin