GSG1L-containing AMPA receptors are complexes with unique spatiotemporal expression, subunit composition and gating properties

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 the GSG1L-containing AMPAR complex. Here, we show that GSG1L’s spatiotemporal expression, native interactome and allosteric sites are distinct. GSG1L generally expresses late during brain development in a cell-type and region-specific manner, finally constituting about 5% of all AMPAR complexes in the adult brain (at adulthood). While GSG1L can co-assemble with cornichon and TARP subunits into AMPAR complexes, it may also form 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 KGK site, shared with TARPs to slow AMPAR desensitization, and a stronger interaction at a novel site that slows recovery from desensitization.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Brain

SUBMITTER: Jochen Schwenk  

LAB HEAD: Prof. Dr. Bernd Fakler

PROVIDER: PXD044621 | Pride | 2024-01-26

REPOSITORIES: Pride