Direct visualization of myosin-binding protein C bridging myosin and actin filaments in intact muscle

Myosin-binding protein C (MyBP-C) is a thick filament protein playing an essential role in muscle contraction, and MyBP-C mutations cause heart and skeletal muscle disease in millions worldwide. Despite its discovery 40 y ago, the mechanism of MyBP-C function remains unknown. In vitro studies sugges...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 108; no. 28; pp. 11423 - 11428
Main Authors Luther, Pradeep K, Winkler, Hanspeter, Taylor, Kenneth, Zoghbi, Maria E, Craig, Roger, Padrón, Raúl, Squire, John M, Liu, Jun
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 12.07.2011
National Acad Sciences
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Summary:Myosin-binding protein C (MyBP-C) is a thick filament protein playing an essential role in muscle contraction, and MyBP-C mutations cause heart and skeletal muscle disease in millions worldwide. Despite its discovery 40 y ago, the mechanism of MyBP-C function remains unknown. In vitro studies suggest that MyBP-C could regulate contraction in a unique way--by bridging thick and thin filaments--but there has been no evidence for this in vivo. Here we use electron tomography of exceptionally well preserved muscle to demonstrate that MyBP-C does indeed bind to actin in intact muscle. This binding implies a physical mechanism for communicating the relative sliding between thick and thin filaments that does not involve myosin and which could modulate the contractile process.
Bibliography:http://dx.doi.org/10.1073/pnas.1103216108
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Edited* by Hugh E. Huxley, Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA, and approved May 11, 2011 (received for review February 26, 2011)
Author contributions: P.K.L. designed research; P.K.L., R.C., R.P., and J.L. performed research; H.W. and K.T. contributed new reagents/analytic tools; P.K.L., H.W., K.T., M.E.Z., R.C., R.P., J.M.S., and J.L. analyzed data; and P.K.L. and R.C. wrote the paper.
3Present address: Department of Pathology and Laboratory Medicine, University of Texas Medical School, 6431 Fannin Street, Houston, TX 77030.
2Present address: Cell Physiology and Molecular Biophysics, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX 79430.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1103216108