To understand molecular interactions that organize developing myofibrils, we examined the biosynthesis and interaction of titin and myosin heavy chain in cultures of developing muscle. Use of pulse-labeling, immunoprecipitation, and a reversible cross-linking procedure demonstrates that within minutes of synthesis, titin and myosin heavy chain can be chemically cross-linked into very large, detergent-resistant complexes retaining many features of intact myotubes. These complexes, predominantly of titin and myosin, occur very early in myofibrillogenesis as well as later. These data suggest that synthesis and assembly of titin and myosin are temporally and spatially coordinated in nascent myofibrils and support the hypothesis that titin molecules help to organize sarcomere formation.
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http://dx.doi.org/10.1073/pnas.89.16.7496 | DOI Listing |
J Mol Cell Cardiol Plus
June 2024
Division of Pulmonary Circulation, Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.
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View Article and Find Full Text PDFEgypt Heart J
January 2025
Department of Physiology, Faculty of Basic Medical Sciences, Obafemi Awolowo College of Health Sciences, Olabisi Onabanjo University, Sagamu Campus, Sagamu, Ogun State, Nigeria.
Background: Hypertrophic cardiomyopathy (HCM) is a frequently encountered cardiac condition worldwide, often inherited, and characterized by intricate phenotypic and genetic manifestations. The natural progression of HCM is diverse, largely due to mutations in the contractile and relaxation proteins of the heart. These mutations disrupt the normal structure and functioning of the heart muscle, particularly affecting genes that encode proteins involved in the contraction and relaxation of cardiac muscle.
View Article and Find Full Text PDFRev Cardiovasc Med
December 2024
Liver Unit, University of Calgary Cumming School of Medicine, Calgary, AB T2N 4N1, Canada.
J Gen Physiol
January 2025
Chemistry Department, University of Massachusetts Lowell, Lowell, MA, USA.
Titin is the third contractile filament in the sarcomere, and it plays a critical role in sarcomere integrity and both passive and active tension. Unlike the thick and thin filaments, which are polymers of myosin and actin, respectively, titin is a single protein that spans from Z-disk to M-line. The N2A region within titin has been identified as a signaling hub for the muscle and is shown to be involved in multiple interactions.
View Article and Find Full Text PDFFront Physiol
December 2024
Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, OH, United States.
Heart failure with preserved ejection fraction (HFpEF) is a major public health challenge, affecting millions worldwide and placing a significant burden on healthcare systems due to high hospitalization rates and limited treatment options. HFpEF is characterized by impaired cardiac relaxation, or diastolic dysfunction. However, there are no therapies that directly treat the primary feature of the disease.
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