Etiology of genetic muscle disorders induced by mutations in fast and slow skeletal MyBP-C paralogs.
Etiology of genetic muscle disorders induced by mutations in fast and slow skeletal MyBP-C paralogs.
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DOI：
10.1038/s12276-023-00953-x
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发表时间：
2023-03
影响因子：
12.8
通讯作者：
Sadayappan, Sakthivel
中科院分区：
文献类型：
--
作者：
Song, Taejeong;Landim-Vieira, Maicon;Ozdemir, Mustafa;Gott, Caroline;Kanisicak, Onur;Pinto, Jose Renato;Sadayappan, Sakthivel
骨骼肌是真核生物系统中高度复杂的肌肉类型，其特征在于与特定肌球蛋白亚型相关的不同肌肉亚型和功能。因此，骨骼肌是许多疾病的目标，包括远端关节弯曲（DA）。在临床上，DA是一种独特的疾病，其特征是在两个或多个远端肢体关节中存在挛缩的变化，而没有神经系统问题。DA是遗传性的，高达40%的患有这种疾病的患者在编码肌节蛋白的基因中存在突变，包括肌球蛋白重链、肌钙蛋白和原肌球蛋白，以及肌球蛋白结合蛋白-C（MYBPC）。我们的研究小组和其他人正在积极研究MYBPC在骨骼肌中的具体作用。MYBPC蛋白质家族在横纹肌的收缩中起着关键作用。更具体地，存在MYBPC基因的三种旁系同源物，并且这些旁系同源物因其在慢骨骼肌、快骨骼肌和心肌中的主要表达而分别命名为sMyBP-C、fMyBP-C和cMyBP-C，并且分别由MYBPC 1、MYBPC 2和MYBPC 3基因编码。虽然各种类型的骨骼肌疾病的生理学是明确的，但DA的病理调节的分子机制仍有待阐明。在这篇综述文章中，我们的目的是强调最近的发现，涉及骨骼肌特异性sMyBP-C和fMyBP-C的作用，以及它们的表达谱，在肌节中的定位，以及在调节肌肉收缩性中的潜在作用。本文就MYBPC骨骼肌旁系同源物的研究进展、其在骨骼肌功能中的作用以及未来的研究方向作一综述。心脏和骨骼肌的收缩和舒张都受到不同形式的MyBP-C蛋白质的调节，这种蛋白质的突变是心脏和骨骼肌疾病的重要原因。虽然心脏的形式已经得到了很好的研究，但两种骨骼形式还没有得到很好的理解。美国辛辛那提大学的Taejeong Song和Sakthivel Sadayappan回顾了目前对MyBP-C蛋白的结构和功能以及突变与疾病之间联系的理解。他们报告说，心脏形式的突变是肥厚型心肌病（心肌疾病）的最常见原因。骨骼肌MyBP-C的突变与肌肉疾病有关，如远端关节挛缩、手部和足部挛缩，这些疾病会使关节僵硬并降低活动性。对MyBP-C功能的进一步研究可能有助于开发基因疗法。
Skeletal muscle, a highly complex muscle type in the eukaryotic system, is characterized by different muscle subtypes and functions associated with specific myosin isoforms. As a result, skeletal muscle is the target of numerous diseases, including distal arthrogryposes (DAs). Clinically, DAs are a distinct disorder characterized by variation in the presence of contractures in two or more distal limb joints without neurological issues. DAs are inherited, and up to 40% of patients with this condition have mutations in genes that encode sarcomeric protein, including myosin heavy chains, troponins, and tropomyosin, as well as myosin binding protein-C (MYBPC). Our research group and others are actively studying the specific role of MYBPC in skeletal muscles. The MYBPC family of proteins plays a critical role in the contraction of striated muscles. More specifically, three paralogs of the MYBPC gene exist, and these are named after their predominant expression in slow-skeletal, fast-skeletal, and cardiac muscle as sMyBP-C, fMyBP-C, and cMyBP-C, respectively, and encoded by the MYBPC1, MYBPC2, and MYBPC3 genes, respectively. Although the physiology of various types of skeletal muscle diseases is well defined, the molecular mechanism underlying the pathological regulation of DAs remains to be elucidated. In this review article, we aim to highlight recent discoveries involving the role of skeletal muscle-specific sMyBP-C and fMyBP-C as well as their expression profile, localization in the sarcomere, and potential role(s) in regulating muscle contractility. Thus, this review provides an overall summary of MYBPC skeletal paralogs, their potential roles in skeletal muscle function, and future research directions. Contraction and relaxation of both heart and skeletal muscles are regulated by different forms of a protein called MyBP-C, mutations in this protein being important causes of heart and skeletal muscle diseases. Although the cardiac form has been well studied, the two skeletal forms are not well understood. Taejeong Song and Sakthivel Sadayappan at the University of Cincinnati, USA, have reviewed current understanding of the structure and function of MyBP-C proteins, and links between mutations and disease. They report that mutations in the cardiac form are the most common cause of hypertrophic cardiomyopathy, disease of the heart muscle. Mutations in skeletal MyBP-C are associated with muscle diseases such as distal arthrogryposes, contracture hands and feet that stiffens joints and reduces mobility. Further study of MyBP-C function may help in developing gene therapies.
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影响因子：
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作者：
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通讯作者：
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4.4
作者：
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通讯作者：
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