McNamara, James W and Li, Amy and Smith, Nicola J and Lal, Sean and Graham, Robert M and Kooiker, Kristina Bezold and van Dijk, Sabine J and Remedios, Cristobal G Dos and Harris, Samantha P and Cooke, Roger (2016) Ablation of cardiac myosin binding protein-C disrupts the super-relaxed state of myosin in murine cardiomyocytes. Journal of Molecular and Cellular Cardiology, 94. pp.65-71. ISSN 1095-8584 (PMC OA)
Full text not available from this repository.Abstract
Cardiac myosin binding protein-C (cMyBP-C) is a structural and regulatory component of cardiac thick filaments. It is observed in electron micrographs as seven to nine transverse stripes in the central portion of each half of the A band. Its C-terminus binds tightly to the myosin rod and contributes to thick filament structure, while the N-terminus can bind both myosin S2 and actin, influencing their structure and function. Mutations in the MYBPC3 gene (encoding cMyBP-C) are commonly associated with hypertrophic cardiomyopathy (HCM). In cardiac cells there exists a population of myosin heads in the super-relaxed (SRX) state, which are bound to the thick filament core with a highly inhibited ATPase activity. This report examines the role cMyBP-C plays in regulating the population of the SRX state of cardiac myosin by using an assay that measures single ATP turnover of myosin. We report a significant decrease in the proportion of myosin heads in the SRX state in homozygous cMyBP-C knockout mice, however heterozygous cMyBP-C knockout mice do not significantly differ from the wild type. A smaller, non-significant decrease is observed when thoracic aortic constriction is used to induce cardiac hypertrophy in mutation negative mice. These results support the proposal that cMyBP-C stabilises the thick filament and that the loss of cMyBP-C results in an untethering of myosin heads. This results in an increased myosin ATP turnover, further consolidating the relationship between thick filament structure and the myosin ATPase.
| Item Type: | Article |
|---|---|
| Additional Information: | Article available free from PMC website |
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 04 Apr 2016 00:27 |
| Last Modified: | 07 Jun 2017 22:39 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/409 |
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