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Cardiac myosin binding protein-C plays no regulatory role in skeletal muscle structure and function
Brian Lin1, Suresh Govindan, Kyounghwan Lee
1Department of Cell and Molecular Physiology, Health Sciences Division, Loyola University Chicago, Maywood, Illinois, USA.
Insights
Cardiac myosin binding protein-C (cMyBP-C) is not essential for adult skeletal muscle development or function. Skeletal muscle isoforms can compensate in the heart, but cMyBP-C absence doesn't prevent cardiac dysfunction.
Area of Science:
- Muscle physiology and molecular biology.
- Cardiac and skeletal muscle development.
- Myosin binding protein-C isoform regulation.
Background:
- Myosin binding protein-C (MyBP-C) has three isoforms: slow skeletal, fast skeletal, and cardiac (cMyBP-C).
- cMyBP-C is primarily cardiac but transiently expressed in neonatal skeletal muscle.
- The necessity of cMyBP-C for skeletal muscle development is unknown.
Purpose of the Study:
- To investigate the role of cMyBP-C in adult skeletal muscle structure and function.
- To determine if cMyBP-C absence affects MyBP-C isoform expression in skeletal muscle.
- To assess skeletal muscle compensation in cMyBP-C null mice.
Main Methods:
- Utilized a cMyBP-C null mouse model (cMyBP-C((t/t))).
- Analyzed MyBP-C isoform expression in skeletal and cardiac tissues.
- Performed histological, ultrastructural, and functional assessments of skeletal muscles.
- Examined cardiac function in the context of dilated cardiomyopathy.
Main Results:
- Skeletal MyBP-C isoform expression was unaffected in cMyBP-C((t/t)) mice.
- Skeletal muscles showed no structural or functional deficits compared to wild-type.
- Fast MyBP-C expression increased in failing hearts of cMyBP-C((t/t)) mice.
- Skeletal isoforms increased in myopathic skeletal muscles.
Conclusions:
- cMyBP-C is dispensable for adult skeletal muscle development and function.
- Skeletal MyBP-C isoforms can transcomplement in the heart lacking cMyBP-C.
- MyBP-C isoforms are differentially regulated across muscle types and in disease states.
Abstract:
Myosin binding protein-C (MyBP-C) exists in three major isoforms: slow skeletal, fast skeletal, and cardiac. While cardiac MyBP-C (cMyBP-C) expression is restricted to the heart in the adult, it is transiently expressed in neonatal stages of some skeletal muscles. However, it is unclear whether this expression is necessary for the proper development and function of skeletal muscle. Our aim was to determine whether the absence of cMyBP-C alters the structure, function, or MyBP-C isoform expression in adult skeletal muscle using a cMyBP-C null mouse model (cMyBP-C((t/t))). Slow MyBP-C was expressed in both slow and fast skeletal muscles, whereas fast MyBP-C was mostly restricted to fast skeletal muscles. Expression of these isoforms was unaffected in skeletal muscle from cMyBP-C((t/t)) mice. Slow and fast skeletal muscles in cMyBP-C((t/t)) mice showed no histological or ultrastructural changes in comparison to the wild-type control. In addition, slow muscle twitch, tetanus tension, and susceptibility to injury were all similar to the wild-type controls. Interestingly, fMyBP-C expression was significantly increased in the cMyBP-C((t/t)) hearts undergoing severe dilated cardiomyopathy, though this does not seem to prevent dysfunction. Additionally, expression of both slow and fast isoforms was increased in myopathic skeletal muscles. Our data demonstrate that i) MyBP-C isoforms are differentially regulated in both cardiac and skeletal muscles, ii) cMyBP-C is dispensable for the development of skeletal muscle with no functional or structural consequences in the adult myocyte, and iii) skeletal isoforms can transcomplement in the heart in the absence of cMyBP-C.
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