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

Link to Article in PubMed

PubMed ID

29422607

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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