Altered interactions among thin filament proteins modulate cardiac function.
Altered interactions among thin filament proteins modulate cardiac function.
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DOI：
10.1006/jmcc.1996.0021
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发表时间：
1996-02
影响因子：
5
通讯作者：
J. Solaro;Jennifer Van Eyk
中科院分区：
文献类型：
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作者：
J. Solaro;Jennifer Van Eyk
心肌肌丝活性从舒张期向收缩期的转变是一个复杂的变构/合作过程，蕴含着丰富的潜在调控机制。转变的速度和强度由肌丝的机械状态、共价和非共价机制以及肌丝蛋白的异构体群体调节。此外，这一过程在病理状态下会发生变化，并可能被用作肌力药物的药理制剂修改。我们在这里介绍了目前对这一过程的看法，重点是细丝成分的分子相互作用，特别是肌钙蛋白I。我们的讨论是根据我们认为在该系统目前的知识状态下迫切需要解决的问题来进行的。这些问题如下：细丝的拓扑结构是什么？细丝蛋白是如何调节跨桥循环的激活的？细丝蛋白的蛋白磷酸化在心脏活动和动力学调节中的相对作用是什么？跨桥结合的反馈效应对细丝活性的相对作用是什么？这些问题的答案具有了新的意义，家族性肥厚型心肌病被确认为一种与肌球蛋白、肌钙蛋白T和原肌球蛋白错义突变有关的“肌球蛋白”疾病。正如所讨论的那样，这一领域令人振奋的新发展使我们更接近这些问题的答案。
The transition of cardiac muscle myofilament activity from the diastolic to the systolic state is a complex allosteric/co-operative process, rich in potential control mechanisms. The rate and intensity of the transition is modulated by the mechanical state of the myofilaments, by covalent and non-covalent mechanisms, and by the isoform population of myofilament proteins. Moreover, the process is altered in pathological states and subject to modification by pharmacological agents with potential use as inotropic drugs. We present here a current perception of the process, with focus on molecular interactions of the thin filament components, especially troponin I. Our discussion is couched in terms of what we believe to be pressing questions in the current state of knowledge of this system. These questions are as follows: what is the topology of the thin filament and how do thin filament proteins regulate the activation of cross-bridge cycling? What is the relative role of protein phosphorylation of thin filament proteins in the regulation of the cardiac activity and dynamics? What is the relative role of feedback effects of cross-bridge binding on thin filament activity? Answers to these questions have taken on new significance, with the identification of familial hypertrophic cardiomyopathy as a "sarcomeric" disease related to missense mutations in myosin, troponin T. and tropomyosin. As discussed, new and exciting developments in this area are bringing us closer to the answers to these questions.