San Diego State University Heart Institute and The Department of Biology, San Diego State University, 5500 Campanile Drive, San Diego, CA 92182, USA.
J Mol Cell Cardiol. 2013 Feb;55:85-91. doi: 10.1016/j.yjmcc.2012.10.006. Epub 2012 Oct 23.
Secreted and membrane proteins play critical roles in myocardial health and disease. Studies in non-myocytes have shown that the peri-nuclear ER is the site for synthesis, folding, and quality control of most secreted and membrane proteins, as well as a nexus of a signal transduction system, called the ER stress response, which informs the cell about the status of ER protein folding. Moreover, the dynamic physical and functional association of the ER with mitochondria is a key site responsible for integrating ER function and mitochondrial metabolism, but is only just beginning to be understood in the myocardium. Although a great deal is known about roles played by the sarcoplasmic reticulum (SR) in contractile calcium handling in the heart, little is known about the relative locations and functions of the peri-nuclear ER and the SR in terms of secreted and membrane protein synthesis and folding. In this review we will explore the current state of knowledge of the location of secreted and membrane protein synthesis, folding, and quality control machinery in cardiac myocytes, as well as our understanding of the functional consequences of ER stress and the unfolded protein response in the heart in terms of protein synthesis, cell growth, and metabolic regulation. This article is part of a Special Issue entitled "Focus on Cardiac Metabolism".
分泌蛋白和膜蛋白在心肌健康和疾病中起着关键作用。在非心肌细胞中的研究表明，核周内质网（ER）是大多数分泌蛋白和膜蛋白合成、折叠和质量控制的场所，也是一个信号转导系统的枢纽，称为内质网应激反应，它可以告知细胞 ER 蛋白折叠的状态。此外，内质网与线粒体之间动态的物理和功能联系是一个关键部位，负责整合内质网功能和线粒体代谢，但在心肌中才刚刚开始被理解。虽然人们对内质网（SR）在心脏收缩钙处理中的作用有了很多了解，但对于核周内质网和 SR 在分泌蛋白和膜蛋白合成和折叠方面的相对位置和功能知之甚少。在这篇综述中，我们将探讨目前关于心脏肌细胞中分泌蛋白和膜蛋白合成、折叠和质量控制机制的位置的知识现状，以及我们对内质网应激和未折叠蛋白反应在心脏中对蛋白合成、细胞生长和代谢调节的功能后果的理解。本文是题为“关注心脏代谢”的特刊的一部分。
