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Updated: Jun 6, 2026

A High-content Assay for Monitoring AMPA Receptor Trafficking
Published on: January 28, 2019
Synaptic targeting of AMPA receptors is regulated by a CaMKII site in the first intracellular loop of GluA1
Wei Lu1, Kaname Isozaki, Katherine W Roche
1Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143, USA.
Abstract:
The accumulation of AMPA receptors (AMPARs) at synapses is essential for excitatory synaptic transmission. However, the mechanisms underlying synaptic targeting of AMPARs remain elusive. We have now used a molecular replacement approach on an AMPAR-null background to investigate the targeting mechanisms necessary for regulating AMPAR trafficking in the hippocampus. Although there is an extensive literature on the role of the GluA1 C-tail in AMPAR trafficking, there is no effect of overexpressing the C-tail on basal transmission. Instead, we found that the first intracellular loop domain (Loop1) of GluA1, a previously overlooked region within AMPARs, is critical for receptor targeting to synapses, but not for delivery of receptors to the plasma membrane. We also identified a CaMKII phosphorylation site (S567) in the GluA1 Loop1, which is phosphorylated in vitro and in vivo. Furthermore, we show that S567 is a key residue that regulates Loop1-mediated AMPAR trafficking. Thus, our study reveals a unique mechanism for targeting AMPARs to synapses to mediate synaptic transmission.
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