Control of AMPA receptor activity by the extracellular loops of auxiliary proteins.

At synapses throughout the mammalian brain, AMPA receptors form complexes with auxiliary proteins, including However, how modulate AMPA receptor gating remains poorly understood. We built structural models of receptor complexes for Tduanyu37s γ2 and γ8, combining recent structural studies and de novo structure predictions. These models, combined with peptide binding assays, provide evidence for multiple interactions between GluA2 and variable extracellular loops of Tduanyu37s. Substitutions and deletions of these loops had surprisingly rich effects on the kinetics of glutamate-activated currents, without any effect on assembly. Critically, by altering the two interacting loops of γ2 and γ8, we could entirely remove all allosteric modulation of GluA2, without affecting formation of AMPA complexes. Likewise, substitutions in the linker domains of GluA2 completely removed any effect of γ2 on receptor kinetics, indicating a dominant role for this previously overlooked site proximal to the AMPA receptor channel gate.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}