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- W4319591750 abstract "AMPA receptor (AMPAR) auxiliary subunits are specialized, non-transient binding partners of AMPARs that modulate their ion channel gating properties and pharmacology, as well as their biogenesis and trafficking. The most well characterized families of auxiliary subunits are transmembrane AMPAR regulatory proteins (TARPs) and cornichon homologs (CNIHs) and the more recently discovered GSG1-L. These auxiliary subunits can promote or reduce surface expression of AMPARs in neurons, thereby impacting their functional role in membrane signaling. Here, we show that CNIH-2 enhances the tetramerization of wild type and mutant AMPARs, possibly by increasing the overall stability of the tetrameric complex, an effect that is mainly mediated by interactions with the transmembrane domain of the receptor. We also find CNIH-2 and CNIH-3 show receptor subunit-specific actions in this regard with CNIH-2 enhancing both GluA1 and GluA2 tetramerization whereas CNIH-3 only weakly enhances GluA1 tetramerization. These results are consistent with the proposed role of CNIHs as endoplasmic reticulum cargo transporters for AMPARs. In contrast, TARP γ-2, TARP γ-8, and GSG1-L have no or negligible effect on AMPAR tetramerization. On the other hand, TARP γ-2 can enhance receptor tetramerization but only when directly fused with the receptor at a maximal stoichiometry. Notably, surface expression of functional AMPARs was enhanced by CNIH-2 to a greater extent than TARP γ-2 suggesting that this distinction aids in maturation and membrane expression. These experiments define a functional distinction between CNIHs and other auxiliary subunits in the regulation of AMPAR biogenesis." @default.
- W4319591750 created "2023-02-09" @default.
- W4319591750 creator A5009908794 @default.
- W4319591750 creator A5013623839 @default.
- W4319591750 creator A5064212412 @default.
- W4319591750 creator A5072982241 @default.
- W4319591750 creator A5083762862 @default.
- W4319591750 date "2023-02-08" @default.
- W4319591750 modified "2023-10-16" @default.
- W4319591750 title "Differential regulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) receptor tetramerization by auxiliary subunits" @default.
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