scholarly journals Myosin binding protein-C slow: a multifaceted family of proteins with a complex expression profile in fast and slow twitch skeletal muscles

2013 ◽  
Vol 4 ◽  
Author(s):  
Maegen A. Ackermann ◽  
Aikaterini Kontrogianni-Konstantopoulos
Keyword(s):  
Expression Profile ◽  
Skeletal Muscles ◽  
Protein C ◽  
Binding Protein ◽  
Myosin Binding Protein ◽  
Myosin Binding Protein C ◽  
Myosin Binding ◽  
Slow Twitch ◽  
Complex Expression

scholarly journals What a drag!: Skeletal myosin binding protein-C affects sarcomeric shortening

2019 ◽  
Vol 151 (5) ◽  
pp. 614-618
Author(s):  
Brett A. Colson
Keyword(s):  
Skeletal Muscle ◽  
Protein C ◽  
Binding Protein ◽  
Functional Effect ◽  
Slow Myosin ◽  
Myosin Binding Protein ◽  
Myosin Binding Protein C ◽  
Skeletal Myosin ◽  
Myosin Binding ◽  
Slow Twitch

Colson discusses a recent investigation of the functional effect of slow myosin binding protein-C in slow-twitch skeletal muscle fibers.

ID: 77: FAST-SKELETAL MYOSIN BINDING PROTEIN-C REGULATES SKELETAL MUSCLE CALCIUM SENSITIVITY

2016 ◽  
Vol 64 (4) ◽  
pp. 917.1-917
Author(s):  
BL Lin ◽  
S Govindan ◽  
S Sadayappan ◽  
L Zhao ◽  
J Xu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Contraction ◽  
Skeletal Muscles ◽  
Protein C ◽  
Molecular Level ◽  
Binding Protein ◽  
Myosin Binding Protein ◽  
Myosin Binding Protein C ◽  
Myosin Binding

Mutations in myosin binding protein-C (MyBP-C) cause both cardiac and skeletal muscle diseases, such as hypertrophic cardiomyopathy and distal arthrogryposis. There are three isoforms of MyBP-C: slow-skeletal, fast-skeletal, and cardiac (ssMyBP-C, fsMyBP-C, and cMyBP-C, respectively). These isoforms reside within the sarcomere, the functional unit of muscle contraction at the molecular level. However, the function of the three major MyBP-C isoforms remains unclear. The present study is the first to focus on the least characterized isoform, fsMyBP-C, which is expressed in fast- and mixed-type skeletal muscles. To determine the necessity of fsMyBP-C for regulation of contraction in the sarcomere, we generated a conventional fast-skeletal MyBP-C knockout (FSKO) mouse model. We analyzed both structural changes and regulatory function of skeletal muscles from heterozygous (FSKO−/+) and homozygous (FSKO−/−), compared to wild-type (WT) mice. Neither heterozygous nor homozygous FSKO mice exhibited changes in morbidity or mortality relative to WT mice. Molecular analyses revealed a complete knockout of fsMyBP-C in the FSKO−/− skeletal muscles compared to FSKO−/+ and WT mice. Histopathological analyses of both Extensor digitorum longus (EDL) and soleus muscles revealed no obvious abnormalities, such as fibrosis or calcification, in either heterozygous or homozygous FSKO mice. Though fiber structure is preserved, we demonstrated that EDL muscles from FSKO−/− mice increases Ca2+-sensitivity of force development, suggesting that fsMyBP-C regulates contraction at the molecular level by decreasing Ca2+-sensitivity. While others have previously proposed the role of cMyBP-C is to increase Ca2+-sensitivity to normalize a Ca2+ gradient imbalance in the heart, we propose that the role of fsMyBP-C in skeletal muscles is to reduce Ca2+-sensitivity of the thin filaments in order to normalize the reversed Ca2+ gradient imbalance. Despite opposite effects on Ca2+-sensitivity, MyBP-C share the same functional role in both cardiac and skeletal muscles. Thus, in addition to elucidating the role of fast-skeletal MyBP-C and its regulation of skeletal muscle contraction, the present study provides insight into the cardiac isoform and its regulation of cardiac contraction.

scholarly journals Myosin Binding Protein-C Slow: An Intricate Subfamily of Proteins

2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
Maegen A. Ackermann ◽  
Aikaterini Kontrogianni-Konstantopoulos
Keyword(s):  
Skeletal Muscles ◽  
Protein C ◽  
Binding Protein ◽  
Thick Filament ◽  
Striated Muscles ◽  
Present Evidence ◽  
Myosin Binding Protein ◽  
Myosin Binding Protein C ◽  
Associated Proteins ◽  
Myosin Binding

Myosin binding protein C (MyBP-C) consists of a family of thick filament associated proteins. Three isoforms of MyBP-C exist in striated muscles: cardiac, slow skeletal, and fast skeletal. To date, most studies have focused on the cardiac form, due to its direct involvement in the development of hypertrophic cardiomyopathy. Here we focus on the slow skeletal form, discuss past and current literature, and present evidence to support that: (i) MyBP-C slow comprises a subfamily of four proteins, resulting from complex alternative shuffling of the single MyBP-C slow gene, (ii) the four MyBP-C slow isoforms are expressed in variable amounts in different skeletal muscles, (iii) at least one MyBP-C slow isoform is preferentially found at the periphery ofM-bands and (iv) the MyBP-C slow subfamily may play important roles in the assembly and stabilization of sarcomericM- andA-bands and regulate the contractile properties of the actomyosin filaments.

scholarly journals The Phosphorylation Profile of Myosin Binding Protein-C Slow is Dynamically Regulated in Slow-Twitch Muscles in Health and Disease

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Maegen A. Ackermann ◽  
Jaclyn P. Kerr ◽  
Brendan King ◽  
Christopher W. Ward ◽  
Aikaterini Kontrogianni-Konstantopoulos
Keyword(s):  
Protein C ◽  
Binding Protein ◽  
Wild Type ◽  
Myosin Binding Protein ◽  
Myosin Binding Protein C ◽  
Phosphorylation Event ◽  
Phosphorylation Pattern ◽  
Health And Disease ◽  
Myosin Binding ◽  
Slow Twitch

Abstract Myosin Binding Protein-C slow (sMyBP-C) is expressed in skeletal muscles where it plays structural and regulatory roles. The functions of sMyBP-C are modulated through alternative splicing and phosphorylation. Herein, we examined the phosphorylation profile of sMyBP-C in mouse slow-twitch soleus muscle isolated from fatigued or non-fatigued young (2-4-months old) and old (~14-months old) wild type and mdx mice. Our findings are two-fold. First, we identified the phosphorylation events present in individual sMyBP-C variants at different states. Secondly, we quantified the relative abundance of each phosphorylation event and of sMyBP-C phospho-species as a function of age and dystrophy, in the presence or absence of fatigue. Our results revealed both constitutive and differential phosphorylation of sMyBP-C. Moreover, we noted a 10–40% and a 25–35% reduction in the phosphorylation levels of select sites in old wild type and young or old mdx soleus muscles, respectively. On the contrary, we observed a 5–10% and a 20–25% increase in the phosphorylation levels of specific sites in young fatigued wild type and mdx soleus muscles, respectively. Overall, our studies showed that the phosphorylation pattern of sMyBP-C is differentially regulated following reversible (i.e. fatigue) and non-reversible (i.e. age and disease) (patho)physiological stressors.

scholarly journals Skeletal Myosin-Binding Protein C Isoforms Differentially Regulate Fast- and Slow-Twitch Skeletal Muscle Function

2020 ◽  
Vol 118 (3) ◽  
pp. 278a
Author(s):  
Shane R. Nelson ◽  
Amy Li ◽  
Sheema Rahmanseresht ◽  
Filip Braet ◽  
Anabelle S. Cornachione ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Function ◽  
Protein C ◽  
Binding Protein ◽  
Skeletal Muscle Function ◽  
Myosin Binding Protein ◽  
Myosin Binding Protein C ◽  
Skeletal Myosin ◽  
Myosin Binding ◽  
Slow Twitch

scholarly journals Erratum: Corrigendum: The Phosphorylation Profile of Myosin Binding Protein-C Slow is Dynamically Regulated in Slow-Twitch Muscles in Health and Disease

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Maegen A. Ackermann ◽  
Jaclyn P. Kerr ◽  
Brendan King ◽  
Christopher W. Ward ◽  
Aikaterini Kontrogianni-Konstantopoulos
Keyword(s):  
Protein C ◽  
Binding Protein ◽  
Myosin Binding Protein ◽  
Myosin Binding Protein C ◽  
Health And Disease ◽  
Myosin Binding ◽  
Slow Twitch

Biological variation of cardiac myosin-binding protein C in healthy individuals

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Bashir Alaour ◽  
Torbjørn Omland ◽  
Janniche Torsvik ◽  
Thomas E. Kaier ◽  
Marit S. Sylte ◽  
...  
Keyword(s):  
Risk Stratification ◽  
Protein C ◽  
Myocardial Injury ◽  
Binding Protein ◽  
Biological Variation ◽  
Cardiac Myosin ◽  
Analytical Quality ◽  
Myosin Binding Protein ◽  
Myosin Binding Protein C ◽  
Myosin Binding

Abstract Objectives Cardiac myosin-binding protein C (cMyC) is a novel biomarker of myocardial injury, with a promising role in the triage and risk stratification of patients presenting with acute cardiac disease. In this study, we assess the weekly biological variation of cMyC, to examine its potential in monitoring chronic myocardial injury, and to suggest analytical quality specification for routine use of the test in clinical practice. Methods Thirty healthy volunteers were included. Non-fasting samples were obtained once a week for ten consecutive weeks. Samples were tested in duplicate on the Erenna® platform by EMD Millipore Corporation. Outlying measurements and subjects were identified and excluded systematically, and homogeneity of analytical and within-subject variances was achieved before calculating the biological variability (CVI and CVG), reference change values (RCV) and index of individuality (II). Results Mean age was 38 (range, 21–64) years, and 16 participants were women (53%). The biological variation, RCV and II with 95% confidence interval (CI) were: CVA (%) 19.5 (17.8–21.6), CVI (%) 17.8 (14.8–21.0), CVG (%) 66.9 (50.4–109.9), RCV (%) 106.7 (96.6–120.1)/−51.6 (−54.6 to −49.1) and II 0.42 (0.29–0.56). There was a trend for women to have lower CVG. The calculated RCVs were comparable between genders. Conclusions cMyC exhibits acceptable RCV and low II suggesting that it could be suitable for disease monitoring, risk stratification and prognostication if measured serially. Analytical quality specifications based on biological variation are similar to those for cardiac troponin and should be achievable at clinically relevant concentrations.

scholarly journals The Interplay between S-glutathionylation and Phosphorylation of Cardiac Troponin I and Myosin Binding Protein C in End-Stage Human Failing Hearts

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1134
Author(s):  
Heidi Budde ◽  
Roua Hassoun ◽  
Melina Tangos ◽  
Saltanat Zhazykbayeva ◽  
Melissa Herwig ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protein C ◽  
Troponin I ◽  
Reduced Glutathione ◽  
Binding Protein ◽  
Enzyme Treatment ◽  
Myosin Binding Protein ◽  
Myosin Binding Protein C ◽  
Myosin Binding ◽  
End Stage

Oxidative stress is defined as an imbalance between the antioxidant defense system and the production of reactive oxygen species (ROS). At low levels, ROS are involved in the regulation of redox signaling for cell protection. However, upon chronical increase in oxidative stress, cell damage occurs, due to protein, DNA and lipid oxidation. Here, we investigated the oxidative modifications of myofilament proteins, and their role in modulating cardiomyocyte function in end-stage human failing hearts. We found altered maximum Ca2+-activated tension and Ca2+ sensitivity of force production of skinned single cardiomyocytes in end-stage human failing hearts compared to non-failing hearts, which was corrected upon treatment with reduced glutathione enzyme. This was accompanied by the increased oxidation of troponin I and myosin binding protein C, and decreased levels of protein kinases A (PKA)- and C (PKC)-mediated phosphorylation of both proteins. The Ca2+ sensitivity and maximal tension correlated strongly with the myofilament oxidation levels, hypo-phosphorylation, and oxidative stress parameters that were measured in all the samples. Furthermore, we detected elevated titin-based myocardial stiffness in HF myocytes, which was reversed by PKA and reduced glutathione enzyme treatment. Finally, many oxidative stress and inflammation parameters were significantly elevated in failing hearts compared to non-failing hearts, and corrected upon treatment with the anti-oxidant GSH enzyme. Here, we provide evidence that the altered mechanical properties of failing human cardiomyocytes are partially due to phosphorylation, S-glutathionylation, and the interplay between the two post-translational modifications, which contribute to the development of heart failure.

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