| 2012 |
GSG1L, a claudin homolog, was identified as a binding protein and auxiliary subunit of AMPA receptors (GluA1-4) through comparative interactome profiling of AMPA and kainate receptor complexes in rat brain, validated by biochemical, cellular, and electrophysiological experiments. GSG1L modulates AMPA-R gating. |
Comparative co-purification/interactome (mass spectrometry), biochemical co-IP, cellular and electrophysiological validation |
Cell reports |
High |
22813734
|
| 2015 |
GSG1L acts as an auxiliary subunit that reduces weighted mean single-channel conductance and calcium permeability of calcium-permeable AMPARs (CP-AMPARs), while increasing polyamine-dependent rectification (promoting inward rectification/polyamine block), in contrast to TARPs which enhance CP-AMPAR function. |
Patch-clamp electrophysiology in recombinant systems and native neurons (cerebellar stellate cells, hippocampal pyramidal neurons); shRNA knockdown and overexpression; mEPSC recordings |
The Journal of neuroscience |
High |
26658868
|
| 2016 |
GSG1L negatively regulates AMPAR-mediated synaptic transmission: overexpression suppresses and GSG1L knockout enhances AMPAR-mediated synaptic transmission in hippocampal CA1 neurons. GSG1L speeds up AMPAR deactivation and desensitization, opposite to effects of TARPs and CNIHs. GSG1L association with AMPARs inhibits CNIH2-induced slowing of receptor kinetics in heterologous cells. Regulation depends on the first extracellular loop domain and the carboxyl-terminus of GSG1L. GSG1L KO rats show deficits in LTP and object recognition. |
GSG1L knockout rats, overexpression, whole-cell patch-clamp electrophysiology, heterologous cell expression, domain deletion mutagenesis |
Nature communications |
High |
26932439
|
| 2016 |
GSG1L regulates the strength of AMPAR-mediated synaptic transmission in hippocampal dentate granule neurons, but does not critically modulate AMPAR deactivation or desensitization kinetics in these cells, demonstrating a neuron-type-specific role. |
Electrophysiology (mEPSC recordings), genetic manipulation in hippocampal dentate granule neurons |
Journal of neurophysiology |
Medium |
27707810
|
| 2017 |
GSG1L specifically chaperones GluA4-containing AMPARs during synaptic delivery in a later stage of classical conditioning in brainstem abducens motor neurons, while TARPγ8 chaperones GluA1-containing AMPARs at an earlier stage, revealing subunit-selective auxiliary protein-mediated AMPAR trafficking. |
Immunofluorescence colocalization, ex vivo brainstem preparation, classical conditioning paradigm |
Neuroscience letters |
Low |
28219790
|
| 2020 |
GSG1L controls short-term plasticity specifically at corticothalamic synapses in anterior thalamus neurons but not at synapses receiving inputs from other pathways. GSG1L KO mice show AT neuron hyperexcitability and increased seizure susceptibility, consistent with GSG1L's negative regulatory role at these synapses. |
GSG1L knockout mice, electrophysiology (synaptic responses in anterior thalamus), seizure susceptibility assays |
Cell reports |
Medium |
32697982
|
| 2021 |
Cryo-EM structures of GluA2 AMPAR in complex with GSG1L reveal that desensitization of GluA2-GSG1L complexes is accompanied by rupture of the ligand-binding domain (LBD) dimer interface. GSG1L binds with maximum stoichiometry of two auxiliary subunits per AMPAR tetramer. The structural mechanism of GSG1L-associated desensitization differs from that of type II TARP γ5 (which maintains two-fold LBD dimer symmetry). |
Cryo-EM structure determination, electrophysiology (single-channel conductance, desensitization kinetics) |
Molecular cell |
High |
34678168
|
| 2023 |
GSG1L acts through two evolutionarily conserved allosteric sites on the AMPAR agonist-binding domain: a weak interaction at the TARP/KGK site that slows desensitization, and a stronger interaction at a distinct site that slows recovery from desensitization. GSG1L can assemble as the sole auxiliary subunit or co-assemble with TARPs or CNIHs, constituting ~5% of AMPAR complexes in the adult brain with region-specific and late developmental expression. |
Native interactome proteomics, single-molecule imaging, electrophysiology, mutagenesis of allosteric sites |
Nature communications |
High |
37884493
|
| 2023 |
GSG1L and γ-2 (stargazin/TARP) compete for the same binding sites on the GluA1 AMPAR tetramer with comparable affinities (apparent Kd ~2.0–2.5/µm²), suggesting their occupancy is dynamically regulated by relative expression levels. |
Three-color single-molecule fluorescence imaging in living cells, quantitative colocalization analysis |
Cellular & molecular biology letters |
Medium |
37430208
|
| 2025 |
Intracellular spermine (polyamine) is required for GSG1L's characteristic suppression of CP-AMPAR single-channel conductance and its slowing of recovery from desensitization. Without intracellular spermine, GSG1L loses these effects. Specific residues in the channel selectivity filter and in GSG1L's C-tail are required for these polyamine-dependent effects. TARPs prevent spermine-mediated conductance reduction whereas GSG1L enhances it. |
Patch-clamp electrophysiology with intracellular spermine manipulation, site-directed mutagenesis of channel selectivity filter residues and GSG1L C-tail |
The Journal of neuroscience |
High |
40185633
|