The Giant Protein Titin’s Role in Cardiomyopathy: Genetic, Transcriptional, and Post-translational Modifications of TTN and Their Contribution to Cardiac Disease
Year: 2019
Type: review
Abstract: mutations in development of DCM, how differential expression of titin isoforms relate to DCM pathophysiology, and discuss how post-translational modifications of titin can affect cardiomyocyte function. Current research efforts aim to elucidate the contribution of titin to myofibril assembly, stability, and signal transduction, and how mutant titin leads to cardiac dysfunction and human disease. Future research will need to translate this knowledge toward novel therapeutic approaches that can modulate titin transcriptional and post-translational defects to treat DCM and heart failure. HIGHLIGHTS: - Titin (TTN) truncation variants are the most frequent cause of dilated cardiomyopathy, one of the main causes of heart failure and heart transplant. Titin is a giant protein, and the mechanisms causing the disease are both complex and still incompletely understood.- This review discusses the role of titin in myocardial function and in disease. In particular, we discuss TTN gene structure, the complexity of genotype-phenotype correlation in human disease, the physiology of TTN and the role of post-translation modification.- Additional studies will be required to clarify whether missense variants are associated with cardiac disease. While initial studies suggested a role of non-synonymous variants in arrhythmogenic cardiomyopathy, confirmatory investigations have been hampered by the complexity of the protein structure and function.
Source: Frontiers in Physiology
Institutions: University of Colorado Anschutz, University of Trieste
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,950
Awards: G1605632830, Whole genome DNA sequencing to identify novel genes in dilated cardiomyopathy, G252781271, Genetics, Mechanisms and Clinical Phenotypes of Arrhythmogenic Cardiomyopathy, G3579498769, G3665166657, G4146012505, Post Graduate Studies in Cardiovascular Research, Molecular Genetics, Pathogenesis and Protein-Replacement Therapy in Arrhythmogenic Cardiomyopathy, G5299480414, Molecular Epidemiology of Dilated Cardiomyopath
OpenAlex ID: W2989618514