Department of Cell and Developmental Biology
Biophysics | Cardiovascular System | Cell Biology | Cellular and Molecular Physiology
The beating heart exhibits remarkable contractile fidelity over a lifetime, which reflects the tight coupling of electrical, chemical, and mechanical elements within the sarcomere, the elementary contractile unit. On a beat-to-beat basis, calcium is released from the ends of the sarcomere and must diffuse toward the sarcomere center to fully activate the myosin- and actin-based contractile proteins. The resultant spatial and temporal gradient in free calcium across the sarcomere should lead to nonuniform and inefficient activation of contraction. We show that myosin-binding protein C (MyBP-C), through its positioning on the myosin thick filaments, corrects this nonuniformity in calcium activation by exquisitely sensitizing the contractile apparatus to calcium in a manner that precisely counterbalances the calcium gradient. Thus, the presence and correct localization of MyBP-C within the sarcomere is critically important for normal cardiac function, and any disturbance of MyBP-C localization or function will contribute to the consequent cardiac pathologies.
myosin-binding protein C, native thick filaments, native thin filaments, calcium dynamics, phosphorylation, muscle activation, muscle regulation, cardiac excitation-contraction coupling
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Copyright © 2015, The Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
DOI of Published Version
Sci Adv. 2015;1(1). pii: e1400205. Link to article on publisher's site
Previs, Michael J.; Prosser, Benjamin L.; Mun, Ji Young; Previs, Samantha Beck; Gulick, James; Lee, Kyounghwan; Robbins, Jeffrey; Craig, Roger; Lederer, W J.; and Warshaw, David M., "Myosin-binding protein C corrects an intrinsic inhomogeneity in cardiac excitation-contraction coupling" (2015). Cell and Developmental Biology Publications. 174.
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