Department of Cell and Developmental Biology; Department of Radiology; Craig Lab
Biochemistry | Cell Biology | Cellular and Molecular Physiology
Muscle contraction, which is initiated by Ca(2+), results in precise sliding of myosin-based thick and actin-based thin filament contractile proteins. The interactions between myosin and actin are finely tuned by three isoforms of myosin binding protein-C (MyBP-C): slow-skeletal, fast-skeletal, and cardiac (ssMyBP-C, fsMyBP-C and cMyBP-C, respectively), each with distinct N-terminal regulatory regions. The skeletal MyBP-C isoforms are conditionally coexpressed in cardiac muscle, but little is known about their function. Therefore, to characterize the functional differences and regulatory mechanisms among these three isoforms, we expressed recombinant N-terminal fragments and examined their effect on contractile properties in biophysical assays. Addition of the fragments to in vitro motility assays demonstrated that ssMyBP-C and cMyBP-C activate thin filament sliding at low Ca(2+). Corresponding 3D electron microscopy reconstructions of native thin filaments suggest that graded shifts of tropomyosin on actin are responsible for this activation (cardiac > slow-skeletal > fast-skeletal). Conversely, at higher Ca(2+), addition of fsMyBP-C and cMyBP-C fragments reduced sliding velocities in the in vitro motility assays and increased force production in cardiac muscle fibers. We conclude that due to the high frequency of Ca(2+) cycling in cardiac muscle, cardiac MyBP-C may play dual roles at both low and high Ca(2+). However, skeletal MyBP-C isoforms may be tuned to meet the needs of specific skeletal muscles.
Atomic force microscopy, Muscle contraction
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DOI of Published Version
Sci Rep. 2018 Feb 8;8(1):2604. doi: 10.1038/s41598-018-21053-1. Link to article on publisher's site
Lin BL, Li A, Mun J, Previs MJ, Previs SB, Campbell SG, Dos Remedios CG, P. Tombe Pd, Craig R, Warshaw DM, Sadayappan S. (2018). Skeletal myosin binding protein-C isoforms regulate thin filament activity in a Ca(2+)-dependent manner. Radiology Publications and Presentations. https://doi.org/10.1038/s41598-018-21053-1. Retrieved from https://escholarship.umassmed.edu/radiology_pubs/381
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This work is licensed under a Creative Commons Attribution 4.0 License.