Structures of the AMPA receptor in complex with its auxiliary subunit cornichon

Abstract

Regulating synaptic signals In the brain, AMPA-type glutamate receptors (AMPARs) are ion channels that play key roles in synaptic plasticity, cognition, learning, and memory. Two classes of subunits, the claudin family and the cornichon family, regulate AMPAR gating and trafficking. Previous structures have been presented of AMPAR bound to claudin homologs. Now, Nakagawa reports a high-resolution structure of AMPAR bound to the cornichon homolog CNIH3, determined by cryo–electron microscopy (see the Perspective by Schwenk and Fakler). In contrast to a predicted topology of three transmembrane helices and an intracellular amino terminus, CNIH3 has four transmembrane helices, and both the amino and carboxyl termini are extracellular. The structure reveals the architecture of the interaction interface between AMPAR and CNIH3 and suggests a role for lipids in regulating the assembly and function of the AMPAR-CNIH3 complex. Science , this issue p. 1259 ; see also p. 1194