Chang Audrey N, Parvatiyar Michelle S, Potter James D
Department of Molecular and Cellular Pharmacology, University of Miami, Miller School of Medicine, Room 6085A RMSB,1600 NW 10th Avenue, Miami, FL 33136, USA.
Biochem Biophys Res Commun. 2008 Apr 25;369(1):74-81. doi: 10.1016/j.bbrc.2007.12.081. Epub 2007 Dec 26.
The troponin complex was discovered over thirty years ago and since then much insight has been gained into how this complex senses fluctuating levels of Ca(2+) and transmits this signal to the myofilament. Advances in genetics methods have allowed identification of mutations that lead to the phenotypically distinct cardiomyopathies: hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy (RCM) and dilated cardiomyopathy (DCM). This review serves to highlight key in vivo studies of mutation effects that have followed many years of functional studies and discusses how these mutations alter energetics and promote the characteristic remodeling associated with cardiomyopathic diseases. Studies have been performed that examine alterations in signaling and genomic methods have been employed to isolate upregulated proteins, however these processes are complex as there are multiple roads to hypertrophy or dilation associated with genetic cardiomyopathies. This review suggests future directions to explore in the troponin field that would heighten our understanding of the complex regulation of cardiac muscle contraction.
肌钙蛋白复合体是三十多年前发现的，自那时以来，人们对该复合体如何感知钙离子（Ca(2+)）水平的波动并将此信号传递给肌丝有了深入了解。遗传学方法的进展使得能够鉴定出导致表型不同的心肌病的突变：肥厚型心肌病（HCM）、限制型心肌病（RCM）和扩张型心肌病（DCM）。这篇综述旨在强调在多年功能研究之后对突变效应进行的关键体内研究，并讨论这些突变如何改变能量代谢以及促进与心肌病相关的特征性重塑。已经开展了研究来检测信号传导的改变，并采用基因组学方法分离上调的蛋白质，然而这些过程很复杂，因为与遗传性心肌病相关的肥大或扩张有多种途径。这篇综述提出了肌钙蛋白领域未来的探索方向，这将加深我们对心肌收缩复杂调节的理解。
