Details

Autor(en) / Beteiligte

• Lin, Brian Leei
• Li, Amy
• Mun, Ji Young
• Previs, Michael J.
• Previs, Samantha Beck
• Campbell, Stuart G.
• dos Remedios, Cristobal G.
• Tombe, Pieter de P.
• Craig, Roger
• Warshaw, David M.
• Sadayappan, Sakthivel

Titel

Skeletal myosin binding protein-C isoforms regulate thin filament activity in a Ca2+-dependent manner

Ist Teil von

• Scientific reports, 2018-02, Vol.8 (1), p.1-13, Article 2604

Ort / Verlag

London: Nature Publishing Group

Erscheinungsjahr

2018

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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.