Myofilament modulation of contraction.
Myofilament modulation of contraction.
复制标题
肌丝收缩的调节。
DOI：
10.1016/j.abb.2016.05.003
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发表时间：
2016
影响因子：
3.9
通讯作者：
Biesiadecki,BrandonJ
中科院分区：
文献类型：
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作者：
Biesiadecki,BrandonJ
肌球蛋白与肌动蛋白的相互作用是力量和横纹肌收缩发展所必需的。因此，无论是在骨骼肌还是心肌横纹肌，能够与肌动蛋白结合的肌球蛋白分子的数量对肌力的发展至关重要，调节这些分子的数量对于匹配身体的收缩需求与其日常任务至关重要。虽然细胞内钙的增加是启动肌肉收缩所必需的，并可以改变为间接调节肌肉收缩，但正是肌丝调节蛋白对这种增加的钙做出反应，直接调节肌球蛋白分子的数量，这些分子可以结合肌动蛋白，从而发展收缩力量。自从肌丝调节蛋白原肌球蛋白、肌钙蛋白复合体(TN)、肌球蛋白结合蛋白C(MyBP-C)和肌球蛋白调节轻链(RLC)被鉴定以来，人们对这些肌丝调节蛋白的结构和功能及其在调节收缩中的作用已经有了很多了解，但关于肌丝收缩调节的分子机制仍然存在重大问题。本期《生物化学与生物物理学成就》集中了广泛的综述和原创性研究工作，进一步加深了当前对肌丝调节蛋白调节横纹肌收缩的不同分子机制的理解。本期综述总结了关于TN调节复合体将起始钙信号转化为力量及其在调节肌肉收缩中的功能的最新知识。Jonathan Davis及其同事的综述总结了钙作为第二信使信号分子的作用，以及下游传感蛋白通过结合钙来响应这一信号的钙结合基序(1)。这一理解被用来讨论目前关于TN钙传感器如何参与肌肉收缩的肌丝调节的知识，重点是TN复合体肌钙蛋白C(TNC)的钙结合亚单位。最后，综述了设计TNC钙结合EF-Hand基序作为调节肌肉收缩机制的技术现状。Michael Regnier和他的同事的综述总结了TN复合体的钙调节结构-功能，重点是TN抑制亚单位(TnI)的作用(2)。本文就蛋白激酶A(PKA)介导的TnI和TnI肥厚型心肌病相关突变的磷酸化信号如何影响心肌收缩调节的研究现状进行综述。最后，综述了目前支持TNC-TnI相互作用作为调节心脏收缩的肌丝机制的重要作用的现有数据。
The interaction of myosin with actin is necessary to the development of force and striated muscle contraction. Whether in skeletal or cardiac striated muscles, the number of myosin molecules that are able to bind to actin is therefore critical to the development of muscle force and modulating these numbers is essential to match the contractile needs of the body to its everyday tasks. While increased intracellular calcium is required to initiate muscle contraction and can be altered to indirectly modulate muscle contraction, it is the myofilament regulatory proteins that respond to this increased calcium to directly regulate the number of myosin molecules that can bind actin and thus contractile force development. Since the identification of the myofilament regulatory proteins tropomyosin, the troponin complex (Tn), myosin binding protein C (MyBP-C) and the myosin regulatory light chain (RLC), much has been learned about the structure-function of these myofilament regulatory proteins and their role in modulating contraction, however significant questions regarding the molecular mechanism of myofilament contractile modulation remain. This Highlight Issue of Achieves of Biochemistry and Biophysics brings together of a broad spectrum of both reviews and original research works that further the current understanding of the diverse molecular mechanisms involved in the modulation of striated muscle contraction through the myofilament regulatory proteins.Reviews in this Highlight Issue summarize current knowledge regarding the role of the Tn regulatory complex to translate the initiating calcium signal into force and its function in modulating muscle contraction. The review by Jonathan Davis and colleagues summarizes the role of calcium as a second messenger signaling molecule and the calcium binding motifs that the downstream sensing proteins employ to respond to this signal by binding calcium (1). This understanding is applied to discuss current knowledge of how the Tn calcium sensor is involved in the myofilament regulation of muscle contraction with a focus on the calcium binding subunit of the Tn complex troponin C (TnC). Finally, the review addresses current state of the art approaches to engineer the TnC calcium binding EF-hand motif as a mechanism to modulate muscle contraction. The review from Michael Regnier and colleague summarizes the calcium regulated structure-function of the Tn complex with a focus on the role of the Tn inhibitory subunit (TnI)(2). This review discusses current knowledge of how protein kinase A (PKA) mediated phosphorylation signaling to TnI and TnI hypertrophic cardiomyopathy associated mutations affect the modulation of cardiac muscle contraction. Finally, the review addresses current data supporting a significant role for the TnC-TnI interaction as a myofilament mechanism to modulate cardiac contraction.