Department of Cell and Developmental Biology
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.
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Citation: Sci Adv. 2015;1(1). pii: e1400205. Link to article on publisher's site
myosin-binding protein C, native thick filaments, native thin filaments, calcium dynamics, phosphorylation, muscle activation, muscle regulation, cardiac excitation-contraction coupling
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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