Auxiliary subunits highlight a role for the LBD-TMD linkers in glutamate receptor desensitization.

Abstract

Rapid communication between neurons is mediated by the release of neurotransmitters that activate ligand‐gated ion channels at synapses. In the mammalian CNS, most synapses are excitatory and glutamate is the neurotransmitter. There are three pharmacologically defined families of ionotropic glutamate receptors (iGluRs), named after the agonists that selectively activate them: AMPA, NMDA and kainate. Each receptor subtype is a tetrameric, dimer‐of‐dimers, assembly of four pore‐forming subunits that form a cation‐selective ion channel. Although the individual subunits differ for each iGluR subtype, they share a common domain structure: extracellular amino terminal and ligand binding domains (ATD and LBD), a transmembrane pore domain (TMD) with fourfold symmetry, and an intracellular carboxyl terminal domain.