NCX 纯化和克隆 20 年：里程碑。
20 years from NCX purification and cloning: milestones.
机构信息
Department of Physiology and Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095-1760, USA.
出版信息
Adv Exp Med Biol. 2013;961:17-23. doi: 10.1007/978-1-4614-4756-6_2.
Abstract
The Na(+)/Ca(2+) exchanger protein was first isolated from cardiac sarcolemma in 1988 and cloned in 1990. This allowed study of Na(+)/Ca(2+) exchange at the molecular level to begin. I will review the story leading to the cloning of NCX and the research that resulted from this event. This will include structure-function studies such as determination of the numbers of transmembrane segments and topological arrangement. Information on ion transport sites has been gathered from site-directed mutagenesis. The regions involved in Ca(2+) regulation have been identified, analyzed, and crystallized.We have also generated genetically altered mice to study the role of NCX in the myocardium. Of special interest are mice with atrial- or ventricular-specific KO of NCX that reveal new information on the role of NCX in excitation-contraction coupling and in cardiac pacemaker activity.
摘要
Na(+)/Ca(2+) 交换蛋白于 1988 年首次从心肌肌浆网中分离出来，并于 1990 年被克隆。这使得 Na(+)/Ca(2+)交换在分子水平上的研究得以开始。我将回顾导致 NCX 克隆的故事以及由此产生的研究。这将包括结构-功能研究，例如确定跨膜片段的数量和拓扑排列。通过定点突变获得了关于离子转运位点的信息。已经确定、分析和结晶了参与 Ca(2+)调节的区域。我们还通过基因改造生成了小鼠，以研究 NCX 在心肌中的作用。特别有趣的是心房或心室特异性 KO 的 NCX 小鼠，它们揭示了 NCX 在兴奋-收缩偶联和心脏起搏活动中的作用的新信息。
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