Signaling by intracellular β2-adrenergic receptors regulates AMPA receptor trafficking and synaptic plasticity

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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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:Cell Reports
Subjects:
CP: Neuroscience
CP: Cell biology
Online Access:http://www.sciencedirect.com/science/article/pii/S221112472500782X
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Summary: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.
ISSN:2211-1247

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