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 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

scholarly journals HSC70 is a chaperone for wild-type and mutant cardiac myosin binding protein C

JCI Insight ◽  
2018 ◽  
Vol 3 (11) ◽  
Author(s):  
Amelia A. Glazier ◽  
Neha Hafeez ◽  
Dattatreya Mellacheruvu ◽  
Venkatesha Basrur ◽  
Alexey I. Nesvizhskii ◽  
...  
Keyword(s):  
Protein C ◽  
Binding Protein ◽  
Cardiac Myosin ◽  
Wild Type ◽  
Myosin Binding Protein ◽  
Myosin Binding Protein C ◽  
Myosin Binding

scholarly journals Myosin Binding Protein-C Slow in Health and Disease

2019 ◽  
Vol 116 (3) ◽  
pp. 385a-386a
Author(s):  
Janelle Geist ◽  
Janis Stavusis ◽  
Baiba Lace ◽  
Nathan T. Wright ◽  
Christopher W. Ward ◽  
...  
Keyword(s):  
Protein C ◽  
Binding Protein ◽  
Myosin Binding Protein ◽  
Myosin Binding Protein C ◽  
Health And Disease ◽  
Myosin Binding

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.

scholarly journals Phosphomimetic cardiac myosin-binding protein C partially rescues a cardiomyopathy phenotype in murine engineered heart tissue

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Alexander Dutsch ◽  
Paul J. M. Wijnker ◽  
Saskia Schlossarek ◽  
Felix W. Friedrich ◽  
Elisabeth Krämer ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Protein C ◽  
Binding Protein ◽  
Heart Tissue ◽  
Cardiac Myosin ◽  
Wild Type ◽  
Myosin Binding Protein ◽  
Myosin Binding Protein C ◽  
Myosin Binding

AbstractPhosphorylation of cardiac myosin-binding protein C (cMyBP-C), encoded by MYBPC3, increases the availability of myosin heads for interaction with actin thus enhancing contraction. cMyBP-C phosphorylation level is lower in septal myectomies of patients with hypertrophic cardiomyopathy (HCM) than in non-failing hearts. Here we compared the effect of phosphomimetic (D282) and wild-type (S282) cMyBP-C gene transfer on the HCM phenotype of engineered heart tissues (EHTs) generated from a mouse model carrying a Mybpc3 mutation (KI). KI EHTs showed lower levels of mutant Mybpc3 mRNA and protein, and altered gene expression compared with wild-type (WT) EHTs. Furthermore, KI EHTs exhibited faster spontaneous contractions and higher maximal force and sensitivity to external [Ca2+] under pacing. Adeno-associated virus-mediated gene transfer of D282 and S282 similarly restored Mybpc3 mRNA and protein levels and suppressed mutant Mybpc3 transcripts. Moreover, both exogenous cMyBP-C proteins were properly incorporated in the sarcomere. KI EHTs hypercontractility was similarly prevented by both treatments, but S282 had a stronger effect than D282 to normalize the force-Ca2+-relationship and the expression of dysregulated genes. These findings in an in vitro model indicate that S282 is a better choice than D282 to restore the HCM EHT phenotype. To which extent the results apply to human HCM remains to be seen.

scholarly journals Impaired contractile function due to decreased cardiac myosin binding protein C content in the sarcomere

2013 ◽  
Vol 305 (1) ◽  
pp. H52-H65 ◽  
Author(s):  
Y. Cheng ◽  
X. Wan ◽  
T. A. McElfresh ◽  
X. Chen ◽  
K. S. Gresham ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Protein C ◽  
Binding Protein ◽  
Left Ventricular ◽  
Cardiac Myosin ◽  
Wild Type ◽  
Cross Bridge ◽  
Myosin Binding Protein ◽  
Myosin Binding Protein C ◽  
Myosin Binding

Mutations in cardiac myosin binding protein C (MyBP-C) are a common cause of familial hypertrophic cardiomyopathy (FHC). The majority of MyBP-C mutations are expected to reduce MyBP-C expression; however, the consequences of MyBP-C deficiency on the regulation of myofilament function, Ca2+ homeostasis, and in vivo cardiac function are unknown. To elucidate the effects of decreased MyBP-C expression on cardiac function, we employed MyBP-C heterozygous null (MyBP-C+/−) mice presenting decreases in MyBP-C expression (32%) similar to those of FHC patients carrying MyBP-C mutations. The levels of MyBP-C phosphorylation were reduced 53% in MyBP-C+/− hearts compared with wild-type hearts. Skinned myocardium isolated from MyBP-C+/− hearts displayed decreased cross-bridge stiffness at half-maximal Ca2+ activations, increased steady-state force generation, and accelerated rates of cross-bridge recruitment at low Ca2+ activations (<15% and <25% of maximum, respectively). Protein kinase A treatment abolished basal differences in rates of cross-bridge recruitment between MyBP-C+/− and wild-type myocardium. Intact ventricular myocytes from MyBP-C+/− hearts displayed abnormal sarcomere shortening but unchanged Ca2+ transient kinetics. Despite a lack of left ventricular hypertrophy, MyBP-C+/− hearts exhibited elevated end-diastolic pressure and decreased peak rate of LV pressure rise, which was normalized following dobutamine infusion. Furthermore, electrocardiogram recordings in conscious MyBP-C+/− mice revealed prolonged QRS and QT intervals, which are known risk factors for cardiac arrhythmia. Collectively, our data show that reduced MyBP-C expression and phosphorylation in the sarcomere result in myofilament dysfunction, contributing to contractile dysfunction that precedes compensatory adaptations in Ca2+ handling, and chamber remodeling. Perturbations in mechanical and electrical activity in MyBP-C+/− mice could increase their susceptibility to cardiac dysfunction and arrhythmia.

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

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.

Sign in / Sign up

Export Citation Format

Share Document