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Updated: Jul 12, 2025

A High-content Assay for Monitoring AMPA Receptor Trafficking
Published on: January 28, 2019
GSG1L-containing AMPA receptor complexes are defined by their spatiotemporal expression, native interactome and
Amanda M Perozzo1,2, Jochen Schwenk3, Aichurok Kamalova4
1Integrated Program in Neuroscience, McGill University, Montreal, QC, H3A 1A1, Canada.
Abstract:
Transmembrane AMPA receptor regulatory proteins (TARPs) and germ cell-specific gene 1-like protein (GSG1L) are claudin-type AMPA receptor (AMPAR) auxiliary subunits that profoundly regulate glutamatergic synapse strength and plasticity. While AMPAR-TARP complexes have been extensively studied, less is known about GSG1L-containing AMPARs. Here, we show that GSG1L's spatiotemporal expression, native interactome and allosteric sites are distinct. GSG1L generally expresses late during brain development in a region-specific manner, constituting about 5% of all AMPAR complexes in adulthood. While GSG1L can co-assemble with TARPs or cornichons (CNIHs), it also assembles as the sole auxiliary subunit. Unexpectedly, GSG1L acts through two discrete evolutionarily-conserved sites on the agonist-binding domain with a weak allosteric interaction at the TARP/KGK site to slow desensitization, and a stronger interaction at a different site that slows recovery from desensitization. Together, these distinctions help explain GSG1L's evolutionary past and how it fulfills a unique signaling role within glutamatergic synapses.
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