Axial distribution of myosin binding protein-C is unaffected by mutations in human cardiac and skeletal muscle

• Published in: Journal of muscle research and cell motility Vol. 33; no. 1; pp. 61 - 74
• Main Authors: Vydyanath, Anupama, Gurnett, Christina A., Marston, Steve, Luther, Pradeep K.
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.05.2012; Springer Nature B.V
• Subjects: Animal Anatomy; Animals; Arthrogryposis - metabolism; Arthrogryposis - pathology; Biomedical and Life Sciences; Biomedicine; Biopsy; Cardiomyopathy, Hypertrophic - genetics; Cardiomyopathy, Hypertrophic - metabolism; Cardiomyopathy, Hypertrophic - pathology; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell Biology; Connectin; Histology; Humans; Life Sciences; Mice; Microscopy, Electron, Transmission; Morphology; Muscle Proteins - metabolism; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Muscle, Skeletal - ultrastructure; Mutation; Myocardium - metabolism; Myocardium - pathology; Myocardium - ultrastructure; Myosins - genetics; Myosins - metabolism; Original Paper; Protein Binding; Protein Isoforms - genetics; Protein Isoforms - metabolism; Protein Kinases - metabolism; Protein Structure, Tertiary; Proteomics; Rats; Sarcomeres - metabolism; Sarcomeres - pathology; Hypertrophic cardiomyopathy; Thick filament; C-protein; Distal arthrogryposis type 1; MyBP-C; Myosin binding protein-C mutations
• ISSN: 0142-4319; 1573-2657
• DOI: 10.1007/s10974-012-9286-9

Myosin binding protein-C (MyBP-C), a major thick filament associated sarcomeric protein, plays an important functional and structural role in regulating sarcomere assembly and crossbridge formation. Missing or aberrant MyBP-C proteins (both cardiac and skeletal) have been shown to cause both cardiac and skeletal myopathies, thereby emphasising its importance for the normal functioning of the sarcomere. Mutations in cardiac MyBP-C are a major cause of hypertrophic cardiomyopathy (HCM), while mutations in skeletal MyBP-C have been implicated in a disease of skeletal muscle—distal arthrogryposis type 1 (DA-1). Here we report the first detailed electron microscopy studies on human cardiac and skeletal tissues carrying MyBP-C gene mutations, using samples obtained from HCM and DA-1 patients. We have used established image averaging methods to identify and study the axial distribution of MyBP-C on the thick filament by averaging profile plots of the A-band of the sarcomere from electron micrographs of human cardiac and skeletal myopathy specimens. Due to the difficulty of obtaining normal human tissue, we compared the distribution to the A-band structure in normal frog skeletal, rat cardiac muscle and in cardiac muscle of MyBP-C-deficient mice. Very similar overall profile averages were obtained from the C-zones in cardiac HCM samples and skeletal DA-1 samples with MyBP-C gene mutations, suggesting that mutations in MyBP-C do not alter its mean axial distribution along the thick filament.