Figure 3. Regulation of perisynaptic AMPAR trafficking.

We propose that norepinephrine (NE) is shuttled by the amino acid transporter OCT3 localized in the plasma membrane from the cell exterior into the cytosol and then by OCT3 localized in recycling endosomes into their lumen. Here, NE stimulates the β₂ adrenergic receptor (β₂AR) associated with GluA1, which induces PKA activation and phosphorylation of Ser⁸⁴⁵ in GluA1. This phosphorylation event increases surface delivery of AMPARs from recycling endosomes. Lateral diffusion allows AMPARs to reach the PSD, where they are trapped by binding of the C_termini of TARPs to PSD-95. Credit: Kellie Holoski/Science Signaling