气候变化领域集成服务门户(CCPortal): Fast skeletal myosin-binding protein-C regulates fast skeletal muscle contraction

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DOI	10.1073/pnas.2003596118
	Fast skeletal myosin-binding protein-C regulates fast skeletal muscle contraction
	Song T.; McNamara J.W.; Ma W.; Landim-Vieira M.; Lee K.H.; Martin L.A.; Heiny J.A.; Lorenz J.N.; Craig R.; Pinto J.R.; Irving T.; Sadayappan S.
发表日期	2021
ISSN	00278424
卷号	118 期号:17
英文摘要	Fast skeletal myosin-binding protein-C (fMyBP-C) is one of three MyBP-C paralogs and is predominantly expressed in fast skeletal muscle. Mutations in the gene that encodes fMyBP-C, MYBPC2, are associated with distal arthrogryposis, while loss of fMyBP-C protein is associated with diseased muscle. However, the functional and structural roles of fMyBP-C in skeletal muscle remain unclear. To address this gap, we generated a homozygous fMyBP-C knockout mouse (C2−/−) and characterized it both in vivo and in vitro compared to wild-type mice. Ablation of fMyBP-C was benign in terms of muscle weight, fiber type, cross-sectional area, and sarcomere ultrastructure. However, grip strength and plantar flexor muscle strength were significantly decreased in C2−/− mice. Peak isometric tetanic force and isotonic speed of contraction were significantly reduced in isolated extensor digitorum longus (EDL) from C2−/− mice. Small-angle X-ray diffraction of C2−/− EDL muscle showed significantly increased equatorial intensity ratio during contraction, indicating a greater shift of myosin heads toward actin, while MLL4 layer line intensity was decreased at rest, indicating less ordered myosin heads. Interfilament lattice spacing increased significantly in C2−/− EDL muscle. Consistent with these findings, we observed a significant reduction of steady-state isometric force during Ca2+-activation, decreased myofilament calcium sensitivity, and sinusoidal stiffness in skinned EDL muscle fibers from C2−/− mice. Finally, C2−/− muscles displayed disruption of inflammatory and regenerative pathways, along with increased muscle damage upon mechanical overload. Together, our data suggest that fMyBP-C is essential for maximal speed and force of contraction, sarcomere integrity, and calcium sensitivity in fast-twitch muscle. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Contraction; Distal arthrogryposis; Fmybp-C; MYBPC2; Skeletal muscle
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/179739
作者单位	Division of Cardiovascular Health and Disease, Department of Internal Medicine, University of CincinnatiOH 45267, United States; Biophysics Collaborative Access Team, Department of Biological Sciences, Illinois Institute of Technology, Chicago, IL 60616, United States; Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL 32306, United States; Division of Cell Biology and Imaging, Department of Radiology, University of Massachusetts Medical School, Worcester, MA 01655, United States; Department of Pharmacology and Systems Physiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, United States
推荐引用方式 GB/T 7714	Song T.,McNamara J.W.,Ma W.,et al. Fast skeletal myosin-binding protein-C regulates fast skeletal muscle contraction[J],2021,118(17).
APA	Song T..,McNamara J.W..,Ma W..,Landim-Vieira M..,Lee K.H..,...&Sadayappan S..(2021).Fast skeletal myosin-binding protein-C regulates fast skeletal muscle contraction.Proceedings of the National Academy of Sciences of the United States of America,118(17).
MLA	Song T.,et al."Fast skeletal myosin-binding protein-C regulates fast skeletal muscle contraction".Proceedings of the National Academy of Sciences of the United States of America 118.17(2021).