Structure and mechanism of AMPA receptor — auxiliary protein complexes

Ionotropic glutamate receptors in vertebrates are composed of three major subtypes – AMPA, kainate, and NMDA receptors – and mediate the majority of fast excitatory neurotransmission at chemical synapses of the central nervous system. Among the three major families, native AMPA receptors function as complexes with a variety of auxiliary subunits, which in turn modulate receptor trafficking, gating, pharmacology, and permeation. Despite the long history of structure-mechanism studies using soluble receptor domains or intact yet isolated receptors, structures of AMPA receptor-auxiliary subunit complexes have not been available until recent breakthroughs in single-particle cryo-electron microscopy. Single particle cryo-EM studies have, in turn, provided new insights into the structure and organization of AMPA receptor — auxiliary protein complexes and into the molecular mechanisms of AMPA receptor activation and desensitization.