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

ABSTRACT: 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, G_s, 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

SUBMITTER: Lee B 

PROVIDER: S-EPMC12579434 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature