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Post-translational control of cardiac hemodynamics through myosin binding protein C

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Abstract

Cardiac myosin binding protein C (cMyBP-C) is an integral sarcomeric protein that associates with the thick, thin, and titin filament systems in the contractile apparatus. Three different isoforms of MyBP-C exist in mammalian muscle: slow skeletal (MyBPC1), fast skeletal (MyBP-C2, with several variants), and cardiac (cMyBP-C). Genetic screening studies show that mutations in MYBPC3 occur frequently and are responsible for as many as 30–35 % of identified cases of familial hypertrophic cardiomyopathy. The function of cMyBP-C is stringently regulated by its post-translational modification. In particular, the addition of phosphate groups occurs with high frequency on certain serine residues that are located in the cardiac-specific regulatory M domain. Phosphorylation of this domain has been extensively studied in vitro and in vivo. Phosphorylation of the M domain can regulate the manner in which actin and myosin interact, affecting the cross bridge cycle and ultimately, cardiac hemodynamics.

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Acknowledgements

This work was supported by National Heart, Lung and Blood Institute grants P01HL077101, P01HL059408, and R01HL105924 and The Transatlantic Network of Excellence Program grant from Le Fondation Leducq (to J.R.). MKG is a post-doctoral fellow of American Heart Association (Great Rivers Affiliate).

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Correspondence to Jeffrey Robbins.

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Gupta, M.K., Robbins, J. Post-translational control of cardiac hemodynamics through myosin binding protein C. Pflugers Arch - Eur J Physiol 466, 231–236 (2014). https://doi.org/10.1007/s00424-013-1377-y

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  • DOI: https://doi.org/10.1007/s00424-013-1377-y

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