REVIEW ■ : How Glutamate Receptors Are Built

Abstract

Glutamate was shown to excite central neurons almost 40 years ago, but it was not until the mid-1980s that it was widely accepted as a neurotransmitter in the mammalian CNS. In the past decade, the ability to make high-resolution electrophysiological recordings from CNS neurons and the application of molecular biology techniques to the study of glutamate receptors has begun to elucidate the relationship between the structure of these receptors and their functional characteristics. Somewhat surprisingly, these investigations have shown that the ionotropic glutamate receptors make up a novel family of ligand-gated ion channels. Recent work has revealed the protein domains involved in ion permeation and ligand binding, and has begun to identify structural elements involved in channel gating, especially receptor desensitization. Additional se quence motifs have been found that are important for the synaptic localization of glutamate-receptor sub units. Although the subunit composition and stoichiometry of native receptors is still partially unresolved, work over the past decade has shown that the glutamate receptor family exhibits an unexpectedly rich diversity and that the regulation of the structure and function of these receptors is both complex and highly dynamic. NEUROSCIENTIST 5:311-323, 1999