Wu Steven C, OʼConnell Timothy D
Department of Integrative Biology and Physiology, The University of Minnesota, Minneapolis, MN.
J Cardiovasc Pharmacol. 2015 Feb;65(2):91-100. doi: 10.1097/FJC.0000000000000165.
Although convention dictates that G protein-coupled receptors localize to and signal at the plasma membrane, accumulating evidence suggests that G protein-coupled receptors localize to and signal at intracellular membranes, most notably the nucleus. In fact, there is now significant evidence indicating that endogenous alpha-1 adrenergic receptors (α1-ARs) localize to and signal at the nuclei in adult cardiac myocytes. Cumulatively, the data suggest that α1-ARs localize to the inner nuclear membrane, activate intranuclear signaling, and regulate physiologic function in adult cardiac myocytes. Although α1-ARs signal through Gαq, unlike other Gq-coupled receptors, α1-ARs mediate important cardioprotective functions including adaptive/physiologic hypertrophy, protection from cell death (survival signaling), positive inotropy, and preconditioning. Also unlike other Gq-coupled receptors, most, if not all, functional α1-ARs localize to the nuclei in adult cardiac myocytes, as opposed to the sarcolemma. Together, α1-AR nuclear localization and cardioprotection might suggest a novel model for compartmentalization of Gq-coupled receptor signaling in which nuclear Gq-coupled receptor signaling is cardioprotective.
尽管传统观点认为G蛋白偶联受体定位于质膜并在质膜上发挥信号传导作用，但越来越多的证据表明，G蛋白偶联受体定位于细胞内膜并在细胞内膜上发挥信号传导作用，最显著的是细胞核。事实上，现在有大量证据表明，内源性α1肾上腺素能受体（α1-ARs）在成年心肌细胞的细胞核中定位并发挥信号传导作用。总体而言，数据表明α1-ARs定位于内核膜，激活核内信号传导，并调节成年心肌细胞的生理功能。尽管α1-ARs通过Gαq发挥信号传导作用，但与其他Gq偶联受体不同，α1-ARs介导重要的心脏保护功能，包括适应性/生理性肥大、防止细胞死亡（存活信号传导）、正性肌力作用和预处理。同样与其他Gq偶联受体不同，在成年心肌细胞中，大多数（如果不是全部）功能性α1-ARs定位于细胞核，而不是肌膜。总之，α1-ARs的核定位和心脏保护作用可能提示了一种Gq偶联受体信号传导区室化的新模型，其中核Gq偶联受体信号传导具有心脏保护作用。
