title: Nuclear compartmentalization of α1-adrenergic receptor signaling in adult cardiac myocytes.
abstract: 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.
authors.affiliation: Department of Integrative Biology and Physiology, The University of Minnesota, Minneapolis, MN.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Wu
authors.forename: Timothy D
authors.initials: TD
authors.lastname: OʼConnell
mesh_terms: D000328:Adult; D002451:Cell Compartmentation / Q000502:physiology; D002467:Cell Nucleus / Q000502:physiology; D006801:Humans; D032383:Myocytes, Cardiac / Q000502:physiology*; D009685:Nuclear Envelope / Q000378:metabolism*; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D018340:Receptors, Adrenergic, alpha-1; D043562:Receptors, G-Protein-Coupled