ArticleCellular signalling2012
Nuclear localization drives α1-adrenergic receptor oligomerization and signaling in cardiac myocytes.
Article in Cellular signalling, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 80 citations in OpenAlex.
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- Mechanisms of Location Bias in G Protein-Coupled Receptors.Handbook of experimental pharmacology · 2026Review
- GPCR signaling via cAMP nanodomains.The Biochemical journal · 2025Review
- G Protein-Coupled Receptors: A Century of Research and Discovery.Circulation research · 2024Review
- Signalling of Adrenoceptors: Canonical Pathways and New Paradigms.Handbook of experimental pharmacology · 2024Review
- Recent advances on the role of monoamine oxidases in cardiac pathophysiology.Basic research in cardiology · 2023Article
- Nuclear Calcium in Cardiac (Patho)Physiology: Small Compartment, Big Impact.Biomedicines · 2023Review
- Whole-genome resequencing of three Coilia nasus population reveals genetic variations in genes related to immune, vision, migration, and osmoregulation.BMC genomics · 2021Article
- Psychologic Stress Drives Progression of Malignant Tumors via DRD2/HIF1α Signaling.Cancer research · 2021Article
- Predicting Drug-Target Interactions Based on the Ensemble Models of Multiple Feature Pairs.International journal of molecular sciences · 2021Article
- Compartmentalized GPCR Signaling from Intracellular Membranes.The Journal of membrane biology · 2021Review
- Photodynamic Activation of Cholecystokinin 1 Receptor with Different Genetically Encoded Protein Photosensitizers and from Varied Subcellular Sites.Biomolecules · 2020Article
- Angiotensin Receptors Heterodimerization and Trafficking: How Much Do They Influence Their Biological Function?Frontiers in pharmacology · 2020Review
- Coupling to Gq Signaling Is Required for Cardioprotection by an Alpha-1A-Adrenergic Receptor Agonist.Circulation research · 2019Article
- New insights into mechanisms of nuclear translocation of G-protein coupled receptors.Small GTPases · 2019Review
- Calcium/calmodulin regulates signaling at the αEuropean journal of pharmacology · 2019Article
- GPCR signalling from within the cell.British journal of pharmacology · 2018Review
- Intracellular GPCRs Play Key Roles in Synaptic Plasticity.ACS chemical neuroscience · 2018Review
- Subcellular compartmentalization of proximal GαThe Journal of biological chemistry · 2018Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Conventional models of G-protein coupled receptor (GPCR) signaling describe cell surface receptors binding to external ligands, such as hormones or circulating peptides, to induce intracellular signaling and a physiologic response. However, recent studies identify new paradigms indicating that GPCRs localize to and signal at the nucleus and that GPCR oligomers can influence receptor function. Previously, we reported that endogenous α1-adrenergic receptors (α1-ARs) localize to and signal at the nuclei in adult cardiac myocytes. In this study, we examined the mechanisms behind α1-AR nuclear localization and how nuclear localization impacted receptor function. We verified that endogenous α1-ARs localized to the nuclear membrane of intact nuclei isolated from wild-type adult cardiac myocytes. Next, we identified and disrupted putative nuclear localization sequences in both the α1A- and α1B-adrenergic receptors, which led to mis-localization of α1-ARs in cultured adult cardiac myocytes. Using these mutants, we demonstrated that nuclear localization was required for α1-signaling in adult cardiac myocytes. We also found that the nuclear export inhibitor leptomycin B inhibited α1-AR signaling, indicating α1-AR signaling must arise in the nucleus in adult cardiac myocytes. Finally, we found that co-localization of the α1-subtypes at the nuclei in adult cardiac myocytes facilitated the formation of receptor oligomers that could affect receptor signaling. In summary, our data indicate that α1-AR nuclear localization can drive the formation of receptor oligomers and regulate signaling in adult cardiac myocytes.
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Registered trials
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