Signaling by intracellular β2-adrenergic receptors regulates AMPA receptor trafficking and synaptic plasticity
Summary: Signaling by norepinephrine (NE) via adrenergic receptors (ARs) mediates attention, yet the underlying molecular mechanisms are largely unknown. AMPA receptors (AMPARs) form a complex with β2ARs, Gs, adenylyl cyclase, and protein kinase A (PKA) to augment AMPAR phosphorylation and, thereby,...
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| Language: | English |
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Elsevier
2025-08-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S221112472500782X |
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| author | Boram Lee Xiaomin Xing Erik A. Hammes Zhuoer Zeng Zoila M. Estrada-Tobar Karam Kim Kyle E. Ireton Kwun Nok Mimi Man Ariel A. Jacobi Ruben A. Berumen Justin C. Weiner Ao Shen Bing Xu Joanne Wang Paul J. Gasser Manuel F. Navedo Yang K. Xiang Elva Díaz Chao-Yin Chen Mary C. Horne Johannes W. Hell |
| author_facet | Boram Lee Xiaomin Xing Erik A. Hammes Zhuoer Zeng Zoila M. Estrada-Tobar Karam Kim Kyle E. Ireton Kwun Nok Mimi Man Ariel A. Jacobi Ruben A. Berumen Justin C. Weiner Ao Shen Bing Xu Joanne Wang Paul J. Gasser Manuel F. Navedo Yang K. Xiang Elva Díaz Chao-Yin Chen Mary C. Horne Johannes W. Hell |
| author_sort | Boram Lee |
| collection | DOAJ |
| description | Summary: Signaling by norepinephrine (NE) via adrenergic receptors (ARs) mediates attention, yet the underlying molecular mechanisms are largely unknown. AMPA receptors (AMPARs) form a complex with β2ARs, Gs, adenylyl cyclase, and protein kinase A (PKA) to augment AMPAR phosphorylation and, thereby, surface expression. We show that signaling by intracellular β2ARs is required for these effects and two different forms of long-term potentiation (LTP) that depend on β2AR signaling and phosphorylation of the AMPAR GluA1 subunit on S845. Inhibition of two NE transporters, the organic cation transporter 3 (OCT3) and the plasma membrane monoamine transporter (PMAT), impairs phosphorylation of the AMPAR GluA1 subunit on S845 by PKA, GluA1 surface insertion, both forms of LTP, and upregulation of miniature excitatory postsynaptic currents upon injection of NE into neurons. These results provide strong evidence for signaling by NE upon its transport into neurons in general and specifically in synaptic plasticity. |
| format | Article |
| id | doaj-art-c2d07bd1704d4896b0d9cf01e5127aa8 |
| institution | OA Journals |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-c2d07bd1704d4896b0d9cf01e5127aa82025-08-20T02:38:50ZengElsevierCell Reports2211-12472025-08-0144811601110.1016/j.celrep.2025.116011Signaling by intracellular β2-adrenergic receptors regulates AMPA receptor trafficking and synaptic plasticityBoram Lee0Xiaomin Xing1Erik A. Hammes2Zhuoer Zeng3Zoila M. Estrada-Tobar4Karam Kim5Kyle E. Ireton6Kwun Nok Mimi Man7Ariel A. Jacobi8Ruben A. Berumen9Justin C. Weiner10Ao Shen11Bing Xu12Joanne Wang13Paul J. Gasser14Manuel F. Navedo15Yang K. Xiang16Elva Díaz17Chao-Yin Chen18Mary C. Horne19Johannes W. Hell20Department of Pharmacology, University of California, Davis, Davis, CA 95616-8636, USADepartment of Pharmacology, University of California, Davis, Davis, CA 95616-8636, USADepartment of Pharmacology, University of California, Davis, Davis, CA 95616-8636, USADepartment of Pharmacology, University of California, Davis, Davis, CA 95616-8636, USADepartment of Pharmacology, University of California, Davis, Davis, CA 95616-8636, USADepartment of Pharmacology, University of California, Davis, Davis, CA 95616-8636, USADepartment of Pharmacology, University of California, Davis, Davis, CA 95616-8636, USADepartment of Pharmacology, University of California, Davis, Davis, CA 95616-8636, USADepartment of Pharmacology, University of California, Davis, Davis, CA 95616-8636, USADepartment of Pharmacology, University of California, Davis, Davis, CA 95616-8636, USADepartment of Pharmacology, University of California, Davis, Davis, CA 95616-8636, USADepartment of Pharmacology, University of California, Davis, Davis, CA 95616-8636, USADepartment of Pharmacology, University of California, Davis, Davis, CA 95616-8636, USA; VA Northern California Health Care System, Mather, CA 95655, USADepartment of Pharmaceutics, University of Washington, Seattle, WA 98195-7280, USADepartment of Biomedical Sciences, Marquette University, Milwaukee, WI 53201-1881, USADepartment of Pharmacology, University of California, Davis, Davis, CA 95616-8636, USADepartment of Pharmacology, University of California, Davis, Davis, CA 95616-8636, USA; VA Northern California Health Care System, Mather, CA 95655, USADepartment of Pharmacology, University of California, Davis, Davis, CA 95616-8636, USADepartment of Pharmacology, University of California, Davis, Davis, CA 95616-8636, USADepartment of Pharmacology, University of California, Davis, Davis, CA 95616-8636, USADepartment of Pharmacology, University of California, Davis, Davis, CA 95616-8636, USA; Corresponding authorSummary: Signaling by norepinephrine (NE) via adrenergic receptors (ARs) mediates attention, yet the underlying molecular mechanisms are largely unknown. AMPA receptors (AMPARs) form a complex with β2ARs, Gs, adenylyl cyclase, and protein kinase A (PKA) to augment AMPAR phosphorylation and, thereby, surface expression. We show that signaling by intracellular β2ARs is required for these effects and two different forms of long-term potentiation (LTP) that depend on β2AR signaling and phosphorylation of the AMPAR GluA1 subunit on S845. Inhibition of two NE transporters, the organic cation transporter 3 (OCT3) and the plasma membrane monoamine transporter (PMAT), impairs phosphorylation of the AMPAR GluA1 subunit on S845 by PKA, GluA1 surface insertion, both forms of LTP, and upregulation of miniature excitatory postsynaptic currents upon injection of NE into neurons. These results provide strong evidence for signaling by NE upon its transport into neurons in general and specifically in synaptic plasticity.http://www.sciencedirect.com/science/article/pii/S221112472500782XCP: NeuroscienceCP: Cell biology |
| spellingShingle | Boram Lee Xiaomin Xing Erik A. Hammes Zhuoer Zeng Zoila M. Estrada-Tobar Karam Kim Kyle E. Ireton Kwun Nok Mimi Man Ariel A. Jacobi Ruben A. Berumen Justin C. Weiner Ao Shen Bing Xu Joanne Wang Paul J. Gasser Manuel F. Navedo Yang K. Xiang Elva Díaz Chao-Yin Chen Mary C. Horne Johannes W. Hell Signaling by intracellular β2-adrenergic receptors regulates AMPA receptor trafficking and synaptic plasticity Cell Reports CP: Neuroscience CP: Cell biology |
| title | Signaling by intracellular β2-adrenergic receptors regulates AMPA receptor trafficking and synaptic plasticity |
| title_full | Signaling by intracellular β2-adrenergic receptors regulates AMPA receptor trafficking and synaptic plasticity |
| title_fullStr | Signaling by intracellular β2-adrenergic receptors regulates AMPA receptor trafficking and synaptic plasticity |
| title_full_unstemmed | Signaling by intracellular β2-adrenergic receptors regulates AMPA receptor trafficking and synaptic plasticity |
| title_short | Signaling by intracellular β2-adrenergic receptors regulates AMPA receptor trafficking and synaptic plasticity |
| title_sort | signaling by intracellular β2 adrenergic receptors regulates ampa receptor trafficking and synaptic plasticity |
| topic | CP: Neuroscience CP: Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S221112472500782X |
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