In:
Scientific Reports, Springer Science and Business Media LLC, Vol. 8, No. 1 ( 2018-02-08)
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.
Type of Medium:
Online Resource
ISSN:
2045-2322
DOI:
10.1038/s41598-018-21053-1
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2018
detail.hit.zdb_id:
2615211-3
