Nuclear Compartmentalization of alpha 1-Adrenergic Receptor Signaling in Adult Cardiac Myocytes

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 (alpha 1-ARs) localize to and signal at the nuclei in adult cardiac myocytes. Cumulatively, the data suggest that alpha 1-ARs localize to the inner nuclear membrane, activate intranuclear signaling, and regulate physiologic function in adult cardiac myocytes. Although alpha 1-ARs signal through G alpha q, unlike other Gq-coupled receptors, alpha 1-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 alpha 1-ARs localize to the nuclei in adult cardiac myocytes, as opposed to the sarcolemma. Together, alpha 1-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.