title: Titin mutations: the fall of Goliath.
abstract: Titin (TTN), the largest protein in the human body, forms powerful elastic filaments along the sarcomere of cardiomyocytes. This multifunctional protein is involved in numerous cellular processes, including sarcomeric assembly, stabilization and mechanosensing. Along physiological sarcomere lengths, TTN is also the most important determinant of the passive tension of cardiac muscle. However, as the giant Goliath was brought down by David's slingshot, so single-base-pair mutations in the gene encoding TTN (TTN) can ultimately impair to some degree a normal cardiac function. Since the first report on the involvement of TTN mutations in the development of hypertrophic cardiomyopathy, in 1999, dozens of other mutations have been described and associated with the onset of cardiac disease. In this review, we aim to explore some of the mechanisms underlying the functions of TTN, as well as the pathophysiological consequences arising from the expression of abnormal TTN isoforms resulting from mutations located along TTN.
authors.affiliation: Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal.
authors.forename: Manuel
authors.initials: M
authors.lastname: Neiva-Sousa
authors.forename: João
authors.initials: J
authors.lastname: Almeida-Coelho
authors.forename: Inês
authors.initials: I
authors.lastname: Falcão-Pires
authors.forename: Adelino F
authors.initials: AF
authors.lastname: Leite-Moreira
mesh_terms: D009202:Cardiomyopathies / Q000235:genetics / Q000503:physiopathology; D064211:Connectin / Q000235:genetics*; D006801:Humans; D009154:Mutation; D009200:Myocardial Contraction / Q000502:physiology; D032383:Myocytes, Cardiac / Q000502:physiology*
chemical_list: D064211:Connectin; C577285:TTN protein, human