UMMS Affiliation
Department of Cell and Developmental Biology; Department of Radiology; Craig Lab
Publication Date
2018-02-08
Document Type
Article
Disciplines
Biochemistry | Cell Biology | Cellular and Molecular Physiology
Abstract
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.
Keywords
Atomic force microscopy, Muscle contraction
Rights and Permissions
© The Author(s) 2018. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
DOI of Published Version
10.1038/s41598-018-21053-1
Source
Sci Rep. 2018 Feb 8;8(1):2604. doi: 10.1038/s41598-018-21053-1. Link to article on publisher's site
Journal/Book/Conference Title
Scientific reports
Related Resources
PubMed ID
29422607
Repository Citation
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. https://doi.org/10.1038/s41598-018-21053-1. Retrieved from https://escholarship.umassmed.edu/radiology_pubs/381
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.